Could cannabis help to treat autism spectrum disorders?

Autism spectrum disorders (ASDs) are characterized by difficulty with social interaction, repetitive behaviour and limited empathy with peers. Some forms of autism also lead to cognitive and linguistic impairment, although Asperger’s syndrome is an exception to this. So what role does the endocannabinoid system have to play?

 

The EC system is fundamentally linked to autism spectrum disorders

In recent years, a significant body of research has accumulated exploring the link between the endocannabinoid system and ASDs. It has been demonstrated that CB1-receptors are most concentrated in areas in the brain thought to be dysfunctional in cases of autism, namely the cerebellum, hippocampus, and the basal ganglia (Bauman and Kemper 2005Courchesne et al. 2007).

CB1-receptors are concentrated in the cerebellum and hippocampus, which are also associated with ASDs
CB1-receptors are concentrated in the cerebellum and hippocampus, which are also associated with ASDs

As the human foetus develops, CB1-receptors and their associated endocannabinoids play an integral role in neuron differentiation and axonal migration (Fride et al. 2009), processes that are essential for normal neurological development. Furthermore, recent studies suggest that CB1-receptors are responsible for defining the positioning of the synapses themselves (Harkany et al. 2008). It is therefore suggested that activation of CB1-receptors in infancy could trigger ASDs by interrupting normal brain development.

The role of the CB2-receptors in ASDs

The CB2-receptors also have a possible role to play in autism, however. It has been shown that CB2-receptor agonists decrease the rate at which certain important immune cells known as monocytes migrate across the endothelium—the thin layer of cells that separate the circulatory system from the tissues and organs (Rajesh et al.2007). Monocytes are one of the key cell types related to the immune system, and disruption to their deveopment and function has been implicated in the development of ASDs on several occasions (Jyonouchi et al. 2014Entstrom et al. 2010).

A recent study (Siniscalo et al. 2013) demonstrated that in children with autism, levels of CB2-receptors in the monocytes were increased, while levels of CB1-receptors and the anandamide-degrading molecule fatty acid amide hydrolase (FAAH) were unchanged.

The role of acetaminophen/paracetamol in the development of autism

There is evidence to suggest that ASDs could actually be triggered in children by use of paracetamol (acetaminophen), which is believed to exert its analgesic effects by acting on the cannabinoid receptors.

Acetaminophen is deacetylated in the central nervous system to the compound p-aminophenol, which in turn reacts with arachidonic acid (catalysed by FAAH). This reaction produces the compound N-arachidonoylphenolamine (AM404), which inhibits the cellular uptake of anandamide. As a result, anandamide levels increase and produce an analgesic effect.

Furthermore, it has been shown that blocking the CB1-receptors with antagonists completely prevents the analgesic effect of acetaminophen. Thus, it is now known that acetaminophen exerts its effects through degradation to AM404 and activation of the CB1-receptors, although at least one study has indicated that AM404 exerts its effects via the CB1, CB2, and TRPV1 receptors together.

It has been suggested that use of acetaminophen in early childhood may lead to the development of autism by disrupting normal immunological development (Torres 2003). Children who are less able to metabolize acetaminophen may therefore be at increased risk of developing autism, as higher levels of the compound will remain present in the blood for longer periods.

Could the MMR controversy actually be related to paracetamol use?

Indeed, there is substantial evidence indicating that children experiencing fever exhibit fewer and less severe symptoms of autism than in normal times (Curran et al.2007). Furthermore, activation of the CB1-receptors causes a decrease in body temperature, as well as providing an analgesic effect (Fraga et al. 2009).

Interestingly, as the MMR vaccine is known to cause mild fever in some children it is administered to, it has been suggested (Schutlz 2010) that a trigger for the development of autism is in fact the acetaminophen commonly used to treat the fever symptoms, rather than the vaccine itself. Indeed, experiencing fever may be useful to the normal immunological development of a child, and disrupting this process with CB1-receptor agonists may prove to increase the risk of autism developing. However, this hypothesis has not been tested to date.

The possible role of the dopamine signalling system in ASDs

One case study (Dratcu et al. 2007) reports the story of a middle-aged man previously been diagnosed with schizophrenia due to his psychotic symptoms being admitted to an acute psychiatric unit, where for the first time in his life a diagnosis of Asperger’s syndrome was pronounced. Schizophrenia and Asperger’s have many features in common, and the two are often confused due to this.

Monocytes are essential immune cells regulated by the CB2-receptors. Monocyte dysfunction is thought to be a contributing factor to ASDs - Sensi Seeds Blog
Monocytes are essential immune cells regulated by the CB2-receptors. Monocyte dysfunction is thought to be a contributing factor to ASDs (© hasor)

After treatment with the antipsychotic drug aripiprazole, the symptoms of Asperger’s significantly improved. Aripiprazole is a partial agonist at the dopamine D2-receptors, and there is substantial evidence to demonstrate that both schizophrenia and Asperger’s fundamentally involve dopamine dysfunction.

It appears that anandamide may have a part to play in this process. Anandamide is known to play a role in dopaminergic signalling, although the exact mechanism has not been precisely elucidated; however, existing studies (listed in the extensive review, Beltramo et al.2000) indicate that one of the many functions of anandamide within the CNS may be to modulate psychomotor and social activity primary facilitated by the dopamine D2-receptor.

What part does genetics have to play in the development of ASDs?

It was previously believed that the proportion of autism cases attributable to genetic factors was as high as 90%. It is now thought that this was an overestimate due to poorly-designed twin studies, and that the actual heritability of autism is around 30%.

One form of autism, fragile-X sydrome, is the most common monogenic (i.e. caused by a mutation to a single gene or chromosome) cause of inherited autism, and is caused by the inactivation of the FMR1 gene, which is responsible for the production of the FMR protein. It it well-known that the endocannabinoid system is implicated in the regulation of cognitive function, anxiety, perception of pain, susceptibility to seizures, and synaptic plasticity (the ability for synapses to strengthen or weaken depending on their level of activity), all of which are affected in fragile-X.

A study (Busquets-Garcia et al. 2013) investigating the role of the EC system in male mice bred to lack the FMR1 gene found that blocking the CB1-receptors normalized cognitive damage, sensitivity to pain, and susceptibility to seizures, while blocking the CB2-receptors normalized anxiety levels.

So how could ASDs be helped by this?

In recent weeks, much has been made of the recent decision by the Michigan Medical Marijuana Review panel to approve the use of cannabis for ASDs—although the final decision now lies with the Department of Licensing and Regulatory Affairs, which must issue its judgment by late October.

Paracetamol (acetaminophen) indirectly acts on the cannabinoid receptors, and may even be a trigger for ASD if given to children - Sensi Seeds Blog
Paracetamol (acetaminophen) indirectly acts on the cannabinoid receptors, and may even be a trigger for ASD if given to children (© Sam-Cat)

There are various anecdotal examples of children whose autism symptoms are improved with use of medical cannabis—for example, a 9-year-old, severely-autistic boy named Kalel Santiago was recently reported to have spoken his first words after treatment with CBD-rich hemp extract. Just as with epilepsy, it appears that the majority of parents administering cannabis to their autistic children are utilizing CBD-rich oils, apparently with positive results. If activation of the cannabinoid receptors during the child’s development is an underlying cause of ASDs, it stands to reason that administration of antagonists such as CBD would negate this effect.

However, there is also at least one report of autistic children experiencing more significant relief from symptoms when using THC and CBD together. From the existing reports, children who appear to benefit from higher THC ratios are those who suffer from both epilepsy and ASD. There is also one case study of a six-year-old autistic boy whose symptoms were markedly improved by treatment with the synthetic THC analogue dronabinol.

It is important to stress that these are anecdotal results not borne out by rigorous empirical testing to ensure that no other factors are responsible for the apparent effect, and thus it is insufficient for most doctors to comfortably recommend THC-rich medical cannabis products to children, particularly when concerns remain over the effect of THC on the developing brain. Furthermore, the various different types of autism may respond differently to administration of THC, and more research is required to determine exactly what those responses could be.

As research into this particular area of neuroscience intensifies, we will no doubt see the development of targeted therapies to treat the symptoms of ASD in developing children, in an attempt to prevent the disease from intensifying in severity and possibly even to reverse existing neurological damage; it is also likely that we will be able to develop targeted therapies allowing adults diagnosed with ASD to live normal or at least greatly improved lives.

Author: Seshata @ Sensiseeds

10 milestones in the history of medicinal cannabis

The history of medical cannabis is long and turbulent, encompassing almost every corner of the globe and spanning over 6,000 years. Here, we set out what we believe are the most significant milestones on the long march to gain recognition of cannabis as a powerful, effective, and safe medicine.

 

10 milestones in medicinal cannabis FB 0.2

First reference to medical cannabis in Chinese texts

Actually, this first “fact” is of somewhat dubious provenance. It is repeated ad infinitum on cannabis-culture websites that the emperor Shen Nung made the first reference to medical cannabis in the famed herbal treatise, the Pen Ts’ao, which is usually reported to have been written in around 2,500 BCE.

The problem? Well, not only is Shen Nung a legendary figure whom no one is quite sure existed at all, but the book in question is of uncertain age and provenance, and has only existed in its present form since the year 50 CE! However, at this stage most scholars are fairly confident that cannabis was indeed used by the ancient Chinese, and probably before any other civilisation.

Publication of the Sanskrit Ayurvedic texts

Unlike the dates of many early Chinese texts, the Ancient Indians were fairly proactive when it came to dating their historical records, and as a result modern scholars are fairly confident that the first known references to cannabis appear in the Atharvaveda, written in around 1,400 BCE.

The legendary Chinese emperor Shen Nung, who is believed to have popularised medical use of cannabis
The legendary Chinese emperor Shen Nung, who is believed to have popularised medical use of cannabis

In the Atharvaveda, there are multiple references to bhanga, which is well-known (and still continues) to be a common word for cannabis throughout much of Asia and East Africa.

However, it was not until the publication of the works of the physician Susruta sometime prior 800 CE that we have definitive references to medicinal uses of cannabis; in his works, it is described as an anti-phlegmatic.

Arabic medical cannabis

The contribution of medieval Arabic medicine to modern Western forms cannot be underestimated. In around 1100 CE, the principle medical texts of the Islamic Empire began to be translated into Latin and other European languages, forming the basis for medieval and renaissance medicine.

The renowned Persian scholar and physician Ibn-Sina (Latinised as “Avicenna”) was undoubtedly one of the most important contributors to the Arabic medical tradition. His Canon of Medicine (1025 CE) was considered a medical authority for centuries; it contains multiple references to cannabis as a treatment for inflammation, ear infections and skin rashes.

William B. O’Shaughnessy

While dozens of eminent European scholars have expounded the virtues of cannabis over the centuries, from the physicians of Ancient Greece and Rome to the medieval monks of Britain and Germany, the 19th-century Irish surgeon and physician William B. O’Shaughnessy stands out as perhaps the single most important figure in bringing cannabis to attention of Western scholars operating under “modern” principles.

William B. O’Shaughnessy, who is widely credited as introducing C. indica to modern European medicine
William B. O’Shaughnessy, who is widely credited as introducing C. indica to modern European medicine

O’Shaughnessy was employed by the British East India Company in Calcutta between 1833 and 1841, during which time he observed numerous medical benefits of the local Cannabis indica varieties. On his return to England in 1941, he was responsible for the introduction of C. indica into the modern European pharmacopeia, and shortly afterward worked in conjunction with well-known pharmacist Peter Squire to develop and market the first cannabis tincture ever sold in the U.S.

Discovery/isolation of THC & CBD

In 1963, a group of researchers at the Hebrew University in Tel Aviv led by the now-legendary Professor Raphael Mechoulam published a paper entitled “The Structure of Cannabidiol”. This landmark paper marked the first time in modern medical history that a compound uniquely found in cannabis was isolated and identified.

A year later, Mechoulam’s team released a paper entitled “Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish”. This paper outlined the chemical formula and structure of tetrahydrocannabinol, the principal psychoactive compound in cannabis.

Discovery of CBD’s antiepileptic effect

The antiepileptic effect of cannabidiol has been known since at least 1977. That cannabis could in some cases be used to control seizures had been known for some time, certainly by the time of O’Shaughnessy. However, it was not known that CBD was the compound responsible until 1977, when a study into the anticonvulsant effects of THC and CBD compared to and in combination with commonly used anticonvulsants of the time was published.

The study found that CBD but not THC was an “effective and relatively potent anticonvulsant” when administered to rats, and that it enhance the action of numerous other common antiepileptics when administered in conjunction with it.

Discovery of the endocannabinoid system

In 1990, after decades of postulation that the psychoactive molecule THC must act on a specific and unknown protein receptor in the body (just as was found to be the case with cocaine and heroin, which act on the dopamine and opioid receptors respectively), Dr Lisa Matsuda of the National Institute of Mental Health (NIMH) announced that she and her colleagues had successfully identified and cloned just such a receptor.

California's Proposition 215 enabled patients to access safe medicinal cannabis for the first time ever
California’s Proposition 215 enabled patients to access safe medicinal cannabis for the first time ever

The discovery of the cannabinoid receptor type I, or CB1-receptor as it is usually termed, was followed two years later by the discovery of anandamide (the first endogenous cannabinoid, or “endocannabinoid”), and in 1993 by the discovery of the CB2-receptor. Thus, medical science was now aware of an entirely new biological messaging system, which would prove to be of fundamental importance to metabolism and regulation of health.

California implements Proposition 215

In 1996, the voters of the U.S. state of California passed Proposition 215 (“The Compassionate Use Act of 1996”), the first piece of legislation at the state level to specifically permit the use of medicinal cannabis since the drug was effectively outlawed with the passing of the Marihuana Tax Act in 1937.

As a result of Proposition 215, Californians (and now, residents of 22 other states, as well as the District of Columbia) may now access legally-sourced medical cannabis of known provenance and quality.

GW Pharmaceuticals’ Sativex brought to market

The prescription drug Sativex, developed by the British cannabinoid research company GW Pharmaceuticals, is the world’s first whole-plant extract to be successfully developed, approved and marketed for prescription. First licensed in the UK in 2010, Sativex has since become available in a further 28 countries.

GW Pharmaceuticals’ Sativex is the world’s first market-approved whole-plant extract
GW Pharmaceuticals’ Sativex is the world’s first market-approved whole-plant extract

While it represents a significant milestone in the march to legitimise medical cannabis, Sativex has courted significant controversy, as its creators enjoy possession of the only legal license to cultivate cannabis for medical purposes in the UK; meanwhile, the rest of the population continues to be criminalised for cultivation of cannabis, and Sativex is only available in certain locations due to its prohibitive cost.

Discovery of the postulated “entourage effect”

In 2011, Dr Ethan Russo (former senior medical advisor to GW Pharmaceuticals) published an extensive review of the existing research into the interactions between the various cannabinoids and terpenoids found within the cannabis plant. Various studies had already explored many of these interactions, but Russo was the first to coin the term “entourage effect”.

As a result, new focus has been drawn to the importance of studying the synergistic rather than individual effects of the compounds found within the cannabis plant, and has further highlighted the need for legislation which allows for study and medical utilisation of all parts of the cannabis plant, including the psychoactive compound THC.

Author: Seshata @ Sensiseeds

THC can prevent transplanted organs from being rejected

Organ transplants have saved, and continue to save, thousands of lives every day around the world, but ensuring everything goes well is not as easy as it sounds. The main problem we have to tackle is that our bodies are programmed to use our immune system to protect themselves from any external attacks, which includes transplanted organs. Our immune system can trigger a reaction or transplant rejection, which can have fatal consequences. However, the results of a recent study published in the September 2015 issue of the Journal of Leukocyte Biology, suggest that tetrahydrocannabinol or Δ9-THC – one of the best known and best studied cannabinoids, responsible for many, if not most, of the physical and psychoactive effects of cannabis – can help delay the rejection of transplanted organs or tissues in rodents.

The legalisation of medicinal as well as recreational cannabis is a prominent issue in many countries around the world; some have already legalised it while others are in the process of doing so, or discussions regarding this issue are starting. Every day, more studies and scientific research emerges that demonstrate and publicise the numerous benefits, and the undeniable medical and therapeutic benefits of the cannabis plant, and the cannabinoids it contains.

These studies help to dispel the misgivings of those who continue to oppose the legalisation of cannabis, and also highlight the need to make continued progress in scientific research so that such studies may be conducted in a clinical setting, but with human subjects. Some of the more recent studies concern surgery and in this article, we will specifically focus on one of the most interesting ones published last year, adding another benefit to an already long list for cannabis and more specifically the cannabinoid THC.

The THC content of the cannabis plant could help increase the number of lives that can be saved with organ transplants (CC. Prensa 420)
The THC content of the cannabis plant could help increase the number of lives that can be saved with organ transplants (CC. Prensa 420)

The therapeutic value of THC

According to a study titled “Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells” published in 2015 by a group of researchers from the Faculty of Medicine at the University of South Carolina, tetrahydrocannabinol , or THC, one of the main compounds of the cannabis plant, can help delay rejection in incompatible organ transplant patients by activating cannabinoid CB1 receptors in immune cells.

“More and more research is identifying potential beneficial effects of substances contained in marijuana, but a major challenge has been identifying the molecular pathways involved,” said John Wherry, deputy editor of the magazine Journal of Leukocyte Biology in a statement.

Although the ability of THC to regulate the immune system was first identified in the 1970s, today, following a series of tests conducted in rodents, research now suggests that THC may improve the outcome of organ transplants by blocking the immune response that causes the transplanted organs to be rejected.

As a result, more lives could be saved through transplants. Without a doubt, this provides yet even more evidence of the obvious therapeutic potential of cannabis, specifically of THC, which, together with CBD, is the most studied natural cannabinoid.

Organ transplantation: What does it involve?

Organ transplants are one of the most significant examples of scientific progress in medicine today. When an individual’s organs or tissues begin to fail due to illness, it may be necessary to replace the diseased organ or tissue with another one that functions properly. To do so and in order to prolong lives, there needs to be a donor and then subsequently, the recipient’s immune system must not trigger a rejection.

Kidneys, livers, hearts and bone marrow are among the most commonly transplanted organs and tissues. While some organs (such as the heart) can only be donated when the donor has died, others (such as the kidney, liver and bone marrow) can be donated by living donors.

Organs and tissues for transplantation can be donated by living donors (CC. Community of Madrid)
Organs and tissues for transplantation can be donated by living donors (CC. Community of Madrid)

Worldwide, the figures speak for themselves. Every day, hundreds of thousands of people continue to wait for an organ and thousands die while waiting for the arrival of an organ they need to survive. An organ from a donor can save up to 8 lives. Approximately 10% of recipients die while waiting to receive an organ. Each day, more and more people require a transplant to survive.

Transplant rejection: Why does it happen?

Each of us has an individualised immune system, which is affected both by our genetics and the type of environment in which we live throughout our lives. This system recognises foreign bodies and infectious agents, helping to protect us against disease. Agents from outside the body may be infectious (such as bacteria or viruses), but can also be cells that come from another person whose immune system and own individualised response are very different from ours.

Our “innate immunity” does an excellent job in protecting us and is characterised by a rapid response in its first line of defence (such as the skin, our largest organ) against infectious agents, and its ability to stimulate non-specific immune cells that work to destroy potentially harmful substances that have entered the body. We now know that nucleated cells have markers on their surface that are recognised as foreign once they are inoculated or transplanted to another subject. These markers are called histocompatibility antigens (Ag) or transplantation antigens and they provide the tissues of every individual with unique characteristics that differentiate them from others.

But when the failure is so severe that the innate immune system can no longer cope, our “adaptive immunity” comes into play, which is characterised by a more specific, slower, and longer-term response provided by specialised cells (such as T cells and B cells) against agents from outside the body. This is the kind of immunity that comes into play with transplant rejection.

Although, as we already mentioned, organs and tissue transplants currently help to prolong peoples’ lives more than ever before, there are risks involved in the process of receiving organs from the body of another individual. There are several types of rejection, but one of the main problems is that the recipient’s immune system (specifically, their T cells) recognises the new organ or tissue donor as “foreign” and begins to attack and destroy it.

For this reason, it is essential that the recipient’s immune system is as similar as possible to the donor’s, which can be very difficult to coordinate given how unique each individual’s immune system is, and the speed with which organ failure can lead to death. And this is where THC comes in.

The immune system: Can rejection be avoided?

To avoid rejection, the tissue must be examined prior to transplantation in order to identify whether or not the antigens it contains are compatible with the recipient. Although tissue examination ensures the transplanted organ or tissue is as similar as possible to the recipient’s, there is no such thing as 100% compatibility.

No one has antigens that are identical to those of someone else, except in the case of identical twins. For this reason, and once again in order to prevent rejection, it is necessary to use immunosuppressive drugs (which suppress our immune system) so that the body does not always trigger an immune response, thus causing the destruction of the foreign tissue.

Following transplantation, depending on the organ involved, rejection can vary between 30 and 60%, but rejection episodes do not necessarily mean the loss of the organ. However, although more than 90% of acute rejections can be treated successfully with modern immunosuppression treatment, it is important to note that the immunosuppressive drugs currently available to prevent transplant rejection can have harmful side effects themselves, such as diarrhoea, hypertension, acne, weight gain, high cholesterol, high levels of blood sugar, and susceptibility to infection. In addition, they can also increase the risk of dental problems. It is clearly important to find safe alternative treatments.

The demand for organs far exceeds the available supply, so more donations are needed (CC. Magnus D)
The demand for organs far exceeds the available supply, so more donations are needed (CC. Magnus D)

Taking all these factors into consideration, in addition to the fact that demand for organs is far greater than the available supply and that the majority of patients often only have one chance with a donor organ or tissue, transplant rejection can have devastating consequences, which often lead to death.

“According to the United States Department of Health and Human Services, among those who receive a transplant, about 25% of kidney recipients and 40% of heart recipients experience an episode of acute rejection during the first year following transplantation.”(Stanford Medicine).

Organ Transplant rejection: Can THC help prevent it?

To conduct the study in question, researchers administered a placebo and THC to mice that had undergone skin transplant surgery, transplanting the skin of a group of mice to another group of genetically different mice. As already mentioned, incompatible skin was treated with either a placebo or THC, the active cannabis compound.

By injecting donor spleen and skin cells in recipient mice (thus using rodents as models for humans undergoing organ transplant), the researchers found that the recipient mice treated with THC were less likely to reject the new tissue than those that were treated with the placebo. The study showed that by activating CB1receptors, THC helped prevent rejection through several mechanisms:

– preventing an increase in the number of T cell receptors in the recipients’ lymph nodes, thereby reducing the likelihood of a rejection of the donor tissue

– effecting a decrease in inflammatory response signals

– stimulating myeloid suppressor cells, which act to decrease the response of the T cell receptor and prevent rejection

– increasing the duration of the survival of skin cells from donors

It is worth remembering another, previous study published in 2013 in the online magazine Journal of Pharmacology Neuroimmune, which already anticipated how THC could stop the immune reaction that causes the transplanted organs to be rejected, in this case through the CB2 receptors. Although this study only used cell culture models, the researchers observed a dose-dependent effect: higher doses of THC led to higher levels of immunosuppression. In addition, two synthetic cannabinoids were also included, and it was found that they could work just as well. Based on these results, the researchers concluded that cannabinoids are promising in terms of improving the success rate of organ transplants.

Study results: THC as a treatment for transplant rejection

It has been shown that cannabinoids are useful in reducing the inflammatory processes involved in transplant rejection and autoimmune disorders (CC. Kingston Compassion Club Society)
It has been shown that cannabinoids are useful in reducing the inflammatory processes involved in transplant rejection and autoimmune disorders (CC. Kingston Compassion Club Society)

This study by the University of South Carolina joins the growing body of evidence that shows that cannabinoids are useful in modulating and reducing inflammatory processes that are involved not only in transplant rejection but also in autoimmune disorders, cancer and other many serious debilitating diseases.

“Altogether, our research has shown that for the first time, in our understanding, cannabinoid receptors can provide a new method of treatment for graft versus host disease (GVHD) and prevent allograft rejection through the suppression of the immune response in the recipient,” the research team that conducted the study concluded.

Given the serious side effects associated with current treatments used to prevent transplant rejection, along with the very favourable safety profile of THC, the authors say that more effective treatments with fewer side effects are desperately needed. Unfortunately, advances in cannabis-based medicine appear to be driven by the development of synthetic compounds instead of pure scientific discovery.

“These data support the potential of this class of compounds as useful therapies for prolonging graft survival in transplant patients,” said Mitzi Nagarkatti, co-author of the Faculty of Medicine of the University of South Carolina, in a statement.

Medicinal cannabis patients awaiting transplant are adversely affected

It seems incredible and paradoxical that although the THC content of medicinal cannabis can help transplant patients in many countries, patients who use medicinal cannabis to treat a large number of diseases, or relieve their symptoms, may, however, be denied an organ transplant if they test positive for cannabis. This is hugely ironic when it occurs in the United States, where medicinal cannabis is legal in many states.

However, various cases have been publicised by the media, such as that of the doctors at the Cedards-Sinai Medical Centre who informed a 64-year old patient named Norman Smith that they would be taking him off the list of transplant patients until he stops consuming cannabis for at least six months, following his positive test result. They also required him to take part in a treatment program for substance abuse in this period. The irony is that, in that same medical centre, Smith had been given a prescription for medicinal cannabis to help him cope with the adverse effects of chemotherapy treatment for his liver cancer. Unfortunately, Mr. Smith died before being included again in the waiting list for a transplant.

In the United States, medicinal cannabis is legal in many states (CC. torbakhopper)
In the United States, medicinal cannabis is legal in many states (CC. torbakhopper)

The doctors argued that “they had to seriously take into consideration the issue of substance abuse, since it often plays a role in the progression of diseases that may require transplantation, and it may adversely affect a new organ following a transplant.” (Dr. Colquhoun). Again, it is ironic that this statement is not based on scientific evidence, given that cannabis use does not cause organ malfunction or failure.

Moreover, equating the use of a medicinal herb for pain relief in terminal disease with a substance abuse problem seems to be an error in judgment on the part of a healthcare professional. These statements are based purely on stigma and ignorance. Unfortunately, such prejudice from some doctors may have fatal effects on the lives of innocent people; people who are ill and require a transplant as much as other patients in the same situation.

Undoubtedly, there is a need for a change in existing policies that deny access to healthcare for these people, so that cannabis is recognised as a legitimate medicine. Policy makers would do well to take a page out of California’s book, where a law has been passed to protect such patients.

Conclusion

No doubt this study, like many others before it, demonstrates the need for further and more in-depth research into the usefulness of THC in preventing the rejection process in humans. The potential of THC in this field should be explored in order to prolong and save many more lives worldwide – lives that are given a second chance thanks to donations made altruistically by thousands of caring people. Lives which, thanks to THC, could overcome the awful prospect of rejection after receiving a much needed transplant. If only laws did not stand in the way.

Author: Miranda @ Sensiseeds

Endocannabinoids and development: embryos, newborns, breastfeeding and more

The human body benefits from its own network of cannabinoids, called the endocannabinoid system. Especially considering the insanely serious taboo around the cannabis plant and its consumption, the general topic of cannabinoids naturally produced by the human body has been delved into manifold.

 

The topic of endocannabinoids and development has been well-fed as well, despite it being largely kept on the down-low. And perhaps with “reason”; what would legislators have to say about cannabinoids being in large part responsible for some of the very first attempts at survival of human embryos?

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Endocannabinoids: quick rundown of the basics

Cannabinoid receptors (CB) are present in numerous places throughout the human body. On one hand, CB1 receptors are located in many neural and non-neural tissues, notably in the brain, nervous system, digestive system, reproductive system, connective tissues, and glands. CB2 receptors, on the other hand, can be found in non-neural tissue, for instance in the immune system. Benefits brought by these receptors and their allocated cannabinoids are varied, but focused on a single goal: homeostasis, i.e. the capability of an organism to regulate its internal environment to adapt to external parameters.

For instance …
CB1 receptors are known to be the target of the famed cannabinoid THC, but other cannabinoids and endocannabinoids collaborate with CB1 receptors as well, such as anandamide.
CBD, another very popular cannabinoid famed for its multiple therapeutic properties, interacts with both CB1 and CB2 receptors.

Endocannabinoids and development: embryonal implantation

Endocannabinoids are detected in the human body extremely early, before said human body is fully formed in utero. In fact, both CB1 and CB2 receptors are present starting from the early stages of gestation, notably during the process of implantation of the embryo – that is, when the embryo successfully “attaches” itself to the mother/surrogate mother’s uterine wall.

Embryo implantation takes place 6 to 12 days after ovulation. It triggers the providing of oxygen and nutriments from the mother to the embryo in order to allow it to grow.
During that time, the uterus generally registers high levels of anandamide, and requires a very specific and very localized reduction in anandamide levels for the implantation process to succeed, that is, exclusively in the location where the embryo will make the adhesion. [1]

Due to their relation with anandamide, CB1 receptors are at the centre of this process. In case the implantation process is deficient, meaning that the endocannabinoid system is not fulfilling its role, the embryo would fail to survive, making the endocannabinoid anandamide not only important for growth in early stages of gestation, but also capital for the ultimate survival of the embryo.

What does it mean?
The process of embryo implantation is understood in a very limited manner. In particular, the numerous reasons why embryo implantation can fail are not always explainable.
A more in-depth study of anandamide and its effects when provided to the human body from external sources could be of use on the general topic of infertility.
Besides, a more democratic use of this knowledge could also improve odds regarding in vitro fertilization; one major obstacle of such procedures is the failure of the egg to implant itself in the mother’s uterus.

Embryo-in-utero

Endocannabinoids and development: the early post-natal neuronal link

Neural development

Further studies on functionalities managed by CB1 receptors in the brain have shown that these receptors are present in areas that are deserted once the body is at an adult stage.
Indeed, CB1 receptors are not only found in the cerebral cortex and the hippocampus, which are areas in which these receptors are known to be active in adult humans, but in the case of developing brains, also in white matter, notably in the capsula interna and pyramidal tract, as well as in the subventricular zone.
In other words, it is thought that CB1 receptors play a more than crucial role in the early development of the human brain. The receptors are later dismissed by the adult human body once this specific part of the neural development process is completed.
In an attempt to detect the very same process on other species, animal studies conducted on developing brains have also shown the presence of CB1 receptors up until postnatal day 5 in white matter regions such as the corpus callosum, and in the anterior commissure, which both link the two hemispheres of the brain together. [2] [3]

Both sets of results show a transitory presence of cannabinoid receptors in several regions of the developing brain, consistent with the theory that endocannabinoids play a role in brain development.

What does it mean?
Unfortunately, studies conducted on the topic of endocannabinoids and development, especially directly related to the human brain, are far too centred on the basics of this discovery to trigger any sort of concrete application. One could theorize that perhaps one day, certain nervous system-related congenital diseases (such as Cerebral Palsy) could be detected, and possibly treated before their onset.

Neuroprotective properties

Endocannabinoids also seem to have an impact on trauma-induced neuronal loss during a short amount of time after birth.
Experiments conducted postnatally on animals have shown that trauma of external origins responsible for provoking neuronal loss, could be impacted by the protective actions of a synthetic compound emulating THC. In these cases, the THC intake prevented both immediate and delayed neurotoxicity resulting from trauma.
More in depth studying of this process has shown that depending on the exact age of the subject, results could vary; it would appear that the neuroprotective properties provided by CB1 receptors are active only during a short, critical period after birth. [2] [4]

Observations based on this experiment and similar ones have shown a major increase of endocannabinoid anandamide levels following a head trauma. The hypothesis is that anandamide, which interacts with CB1 receptors, could be acting as an endogenous neuroprotectant.

What does it mean?
Evidently, the mammal body already has a way of fending off certain hazards that can occur after birth. Without any trigger other than trauma itself, anandamide protects the very young brain from neuronal loss. However, the THC component, administrated externally, could prove to be an important key element to treating early trauma in newborns. Most of these sources of early trauma are a result of complications in the birthing process, for instance asphyxia or cardiac arrest. However, due to the psychoactive nature of THC, it is likely certain adjustments would be needed. Say, a CBD-THC concoction?

human-brain

Endocannabinoids and development: Suckling response and breastfeeding

Suckling response and failure to thrive

The suckling response in a newborn, i.e. “the [instinctive suckling] of anything that touches the roof of [the] mouth, and simulates the way a child naturally eats”, is a crucial milestone in the human lifecycle. In cases when the newborn survives the absence of feeding response, it can condition future physical developments that can go as far as the adult age, such as growth, general relationship with the feeding process, and their respective by-products (weight gain in relation to age, gastrointestinal difficulties, etc.) It can also have an impact on the mother/caregiver-child relationship, or come from it.

Studies have been trying to prove CB1 receptors are a major parameter in the initiation of the suckling response in newborns. For instance, tests involving the injection of a CB1 receptor antagonist resulted in a failure in milk ingestion, with eventual deaths of the tested subjects a few days later. Such results could only be observed when the antagonist was administrated in the 24 hours following birth, later administration resulting in a smaller to non-existing percentage of consequential deaths. The CB1 receptor antagonist also triggered hypothermia and a lack of motor capabilities to feed. Again, it seems that the endocannabinoid system puts in place temporary coping mechanisms, only to deactivate them when the body does not require them anymore. [2]

What does it mean?
NOFTT, which is a failure to thrive without a known organic source, could be linked to a deficient endocannabinoid system. Despite studies linked having been conducted more than a decade ago, the hypothesis still has not been further studied.

Breastfeeding

The role of certain endocannabinoids in the feeding process of infants was recognized more than two decades ago by various studies. Both anandamide and fellow endocannabinoid 2-arachidonoylglycerol (2-AG) are found in human as well as bovine milk, with a level of 2-AG ten times higher than of anandamide.

Test results suggest that the purpose of 2-AG in the brain is to stimulate the suckling response, and that the resulting milk intake increases its levels, creating over a period of 2 days a pattern of milk suckling behaviour. In cases where an antagonist is administrated, the lack of milk-derived 2-AG results in a failure to develop this pattern, jeopardizing the survival of the breastfeeding subject. [2]

On the other hand, anandamide has been proven to increase food intake. According to scientists, “the underlying circuitry responsible for the therapeutic efficacy of cannabinoids in stimulating appetite is not yet known, although it is probably related to the fact that the CB1 receptor, anandamide, and 2-AG are present in the hypothalamus, which is known to be associated with feeding.” [5]

What does it mean?
Have you ever consumed cannabis recreationally, or medicinally? Have you ever found yourself in the middle of a fit of what is commonly called “the munchies”? If so, you have experienced first-hand the very mechanism that stimulates suckling and appetite, and generally promotes growth and development throughout the human lifecycle.
For reasons ranging from ethics to the current war on drugs, the very sensitive topic of endocannabinoids and development has not yet reached a peak in terms of proliferation of studies, not to mention clinical trials.
Hopefully, recent changes in legislation will result in more consequent funding of cannabinoid research.

Author: Silent Jay @ Sensiseeds

Hemp seed in traditional cooking

Although space brownies and other high-inducing baked goods are the first things most people think of when they consider cannabis cookery, there is a long tradition of cooking with hemp in many regions of the world. Many of these traditions still persist, and are increasing in popularity as the hemp industry regains legitimacy.

 

Hemp butter or 'kanepju pavalgs' is a traditional staple of Latvian cuisine (iecavnieks.lv)
Hemp butter or ‘kanepju pavalgs’ is a traditional staple of Latvian cuisine (iecavnieks.lv)

Hemp in traditional cooking

Non-psychoactive forms of cannabis, generally known as hemp, grow in a great variety of habitats throughout the world. The local inhabitants have utilised hemp seeds in their traditional cooking for countless generations, as they are widely available and cost little to nothing.

Hemp grows abundantly throughout these regions, both under cultivation and in the wild.

Hemp seed has been used for generations by the rural populations of northern Asia and northeast Europe, in China, Mongolia, Russia and Germany and many other present-day nations.

The seeds may be pressed to extract the oil, used whole, or crushed, rolled or ground to produce meal or flour. From these products, a range of porridges, soups, and stews can be created.

Hemp seed can be roughly ground and used to make porridge (Anthimeria)
Hemp seed can be roughly ground and used to make porridge (Anthimeria)

As de-hulling techniques are complex and often require machinery, hemp meals and flours made in rural areas are often gritty and heavy due to the presence of crushed hulls; thus, in times of abundance, other grains are preferred, and hemp is particularly prized in times of famine.

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Hemp in traditional European diets

In medieval Germany and Italy, hemp seeds and oil were used in a variety of cooked dishes, including soups and filled pies. In traditional hemp growing regions of northeast Europe and the Baltic nations, the local hemp seed is still used for oil, and is also used whole or crushed in various other recipes.

In Latvia, hemp seed foods are eaten during annual Midsummer’s Day celebrations in June, which traditionally marked the most significant date in the Latvian calendar. Hemp seeds are also crushed and added to sweet-cream butter to impart a greenish colour and a ‘bitter-fresh and slightly hazy’ flavour. Traditional hemp butter, known as kanepju pavalgs is still widely enjoyed in Latvia today, and is available at most farmers’ markets and health-food stores.

Hemp butter is typically spread on toast or rye bread, or may be used as an additive in various recipes. Reportedly, chefs also use hemp butter as an ingredient in many local dishes, as it is said to impart a pleasant accent to the overall flavour.

Siemieniatka & kanapiø koðë

Siemieniatka or semianka is a soup based on hemp seeds that is still consumed on Christmas Eve in traditional households in Lithuania and Silesia (a historic region now situated in Poland, the Czech Republic and Germany). The soup is made by simmering whole hemp seeds in water until they begin to burst, draining then crushing them thoroughly, whereby a milky, sap-like substance is produced. The hemp-milk is then combined with cow’s milk, flour, salt, sugar and butter and simmered to produce a thick, creamy soup.

A creamy soup made with hemp seeds is still eaten in parts of Poland on Christmas Eve (Stephanski)
A creamy soup made with hemp seeds is still eaten in parts of Poland on Christmas Eve (Stephanski)

In Lithuania, savoury hemp porridge (kanapiø koðë) is traditionally served on potatoes baked in their skins; the porridge is made by dry-frying and grinding hemp seeds to a fine powder, then simmering flour, salt, pepper, and onion in hot water, removing the mixture from the heat, and stirring in the hemp powder. Hemp milk is also used in place of cow’s milk in Lithuania during certain religious festivals.

Hemp cooking in Asia

Locally-produced hemp seed oil has been used as household cooking oil in rural Nepal for generations, and continues to be used to this day. Indeed, hemp seed oil may often represent the sole source of vegetable oil in some remote and isolated populations.

China, which traditionally styled itself the ‘land of hemp and mulberry’, has a long history of hemp foods. Whole hemp seeds are commonly eaten in many parts of China, raw or roasted, and most food markets carry them, particularly in rural areas. Roasted hemp seeds are popular as a snack food in present-day China—they are also on sale at markets food stands in various cities, and are a common ‘family snack’ eaten at outings and events, much as popcorn is in other parts of the world.

Traditional hemp cuisine in Canada

In Canada, cultivation of hemp was widespread by the 19th century, and prospective migrants were even offered free plots of land and hemp seed to cultivate as an incentive. The Doukhobors, a sect of spiritual Christians that arose in 18th-century Russia, migrated en masse to Canada in the late 19th century to escape persecution in their home country. They brought its traditional uses to the newly-established territories along with the seeds themselves, and even after cannabis was outlawed in 1923, it was widely used in soups, cereals and other foods.

The development of modern cuisine

Many of these traditional recipes use whole hemp seeds that still have their hulls intact. The hard shell, which makes up almost 20% of the weight of the seed, is difficult to remove, and flours and meals produced with whole hemp seed often have a gritty, unpleasant texture.

With the tools and techniques available to traditional rural populations, dehulling hemp seed was not an option. However, recent technological advances have enabled a dehulling process that utilises mechanical separation to produce smooth, grit-free hemp seed ‘hearts’, which can be eaten as is, or further processed into fine-textured, light and airy flours and meals.

Hemp foods are increasing in popularity once more, as knowledge of their nutritional value spreads. As well as providing a good basis for a healthy diet, hemp’s various properties can help to ameliorate a range of lifestyle diseases and disorders. While the trend for cooking with medical cannabis has become de rigeur, it is important not to forget the many benefits that hemp cooking can provide.

Author: Seshata @ Sensiseeds

Did you know that other plants produce cannabinoids too?

For years, it was thought that cannabis was the only plant capable of producing cannabinoids. However, in the last few years research has been published that shows that cannabis is not the only plant that produces these compounds, and that they are actually quite common!

 

What exactly is a cannabinoid?

Cannabinoids are lipid-based molecules that all act to some degree on the cannabinoid receptors, which are a primary component of the endocannabinoid system. Cannabinoids are produced by plants (most famously, the cannabis plant), but are also produced by the bodies of humans and most other animal species, and can also be synthesized in laboratories.

Cannabinoids produced by plants are known as phytocannabinoids, those produced by the body are known as endocannabinoids, and lab-synthesized compounds are simply known as synthetic cannabinoids.

Primitive liverworts like this may contain substances related to THC (© Mr & Mrs Apteryx australis)
Primitive liverworts like this may contain substances related to THC (© Mr & Mrs Apteryx australis)

Most cannabis enthusiasts will have heard of the classic cannabinoids such as THC, CBD, THCV and CBC, which for many years were thought to be the only compounds that acted on the cannabinoid receptors. The classic cannabinoids all share the same chemical formula, C21H30O2.

However, as our understanding of the endocannabinoid system has grown, we have found that the number and type of different compounds that act on the receptors is far larger.

Thus, we have to widen the goalposts somewhat as to what constitutes a cannabinoid—beyond the 120 or so classic cannabinoids, there are also an as-yet-undetermined number of related compounds, which also act on the receptors but do not share the classic structure.

And what on earth are cannabimimetics?

This helichrysum contains CBG or related compounds (© plantzafrica.com)
This helichrysum contains CBG or related compounds (© plantzafrica.com)

As well as cannabinoids, we also have an important class of non-classical cannabinoids known as cannabimimetics. They are called cannabimimetics as they literally mimic the biological activity of the classical cannabinoids, despite not sharing their structure.

Cannabimimetics are of increasing importance within the world of medicinal cannabinoid research. Classically, the EC system has been viewed as a simple set of two receptors and two ligands (a ligand is the term for a compound that binds to a receptor).

However, it is now increasingly being shown that the EC system is far more complex than this. Dozens of different compounds are now known to act either directly or indirectly on the EC system, and many of these compounds also work on other important biological messaging systems such as the opioid, serotonergic and dopaminergic signalling systems.

Some examples of known cannabimimetics:

 

NAE’s & N-alkylamides

N-acylethanolamines are a class of fatty acid compounds which are known to be heavily involved in biological signaling. NAE’s include N-arachidonoylethanolamine (better known as anandamide), N-palmitoylethanolamine (PEA), N-linoleoylethanolamide (LEA), and N-oleoylethanolamine (OEA).

Echinacea has been found to contain cannabimimetic N-alkyamides
Echinacea has been found to contain cannabimimetic N-alkyamides

Anandamide is well known for being the biological compound which most closely resembles the activity of THC, as it directly agonizes the principal cannabinoid receptors. It is now also known that anandamide also directly agonizes a third cannabinoid receptor known as GPR119, which is also affected by N-oleoylethanolamine.

As well as directly acting on the principal and minor cannabinoid receptors, NAE’s are also known to exert a range of indirect effects. For example, LEA, PEA and OEA all inhibit levels of the FAAH enzyme that is responsible for degrading anandamide itself, and thus can effectively increase levels of anandamide in tissues over time.

N-alkylamides are a similar but less well-researched class of cannabimimetic compounds that have been shown to exert selective effects on the CB2-receptors, and have been shown to exert anti-inflammatory effects similar to anandamide.

Beta-caryophyllene

This important terpene is found in cannabis, and its oxide (which forms on contact with air) is the compound detected by drug-sniffing dogs! B-caryophyllene has been shown to act as a full agonist of the CB2-receptor, although it does not act on the CB1-receptor.

It has also been shown to exert anti-inflammatory and analgesic effects in mice, but not in mice bred to lack CB2-receptors—showing that this biological activity is exerted via the receptors themselves.

Salvinorin A

Salvinorin A is the main component of the psychoactive plant species Salvia divinorum. Unusually for a hallucinogenic plant compound, salvinorin A is a terpenoid, not an alkaloid like mescaline, psilocybin and DMT. Furthermore, it is a dissociative, rather than a classic hallucinogen.

Interestingly, it seems that salvinorin A does not interact with the classic cannabinoid receptors, but in fact interacts with a putative third cannabinoid receptor that apparently forms only in inflammatory conditions, and which also acts as a kappa-opioid receptor. The κ-opioid receptors are fundamental to pain regulation, and are also the principal target of most hallucinatory compounds!

Myrcene

The Chinese rhododendron has been shown to contain CBC or related compounds
The Chinese rhododendron has been shown to contain CBC or related compounds

Another very important terpene found in cannabis, and one that is also a major constituent of the essential oil of hops. Although it is not thought that myrcene directly acts on the cannabinoid receptors, it is now known that its biological activity alters the psychoactive effect of THC.

Myrcene is known to be present in high levels in strains that exert a ‘stoney’ or ‘couchlock’ effect on the user. The sedative effects of myrcene-containing plants such as hops and verbena have been known for millennia, and it is now thought that the sedative effect is due to myrcene’s ability to agonise (activate) the opioid receptors (studies have shown that the opioid antagonist naxalone blocks myrcene’s effects, suggesting that myrcene is an agonist).

Thus, although myrcene isn’t typically classed as a cannabinoid in the currently existing scientific literature, it certainly affects the subjective experience of the cannabis ‘high’. Further research will no doubt determine the exact nature of the link; presently, while testing labs such as Steep Hill Halent in California have been collecting data on the association for years, no formal studies have as yet been conducted.

Plants that produce ‘cannabimimetic’ compounds

First off, there are abundant plant sources of terpenes such as β-caryophyllene and myrcene, although of course, some sources are better than others. Myrcene is found in extremely high concentrations in hop oil, making up almost 80% of the extracted volume in some varieties, and is also found in high levels in mangoes, lemongrass, thyme, and verbena.

B-caryophyllene is found in black pepper, cloves, rosemary, hops, caraway, oregano, basil, lavender, cinnamon, and many more plant species. In most of these species, β-caryophyllene is a major constituent of the essential oil (comprising 20% in some hop species).

CBD-like compounds were recently discovered in flax seeds
CBD-like compounds were recently discovered in flax seeds

Salvinorin A is much rarer, and appears to only be found in high quantities in S. divinorum itself. However, there are indications that other sage species may also contain traces of the compound itself, or closely related molecules.

NAE’s including OAE, PEA and LEA have been found to occur in many plant species. Notably, OAE and LEA have both been found in the cocoa plant, and black truffles have even been reported to contain anandamide itself! Lastly, the compounds known as N-alkylamides have been found in various echinacea species, and it is thought that echinacea’s importance in herbal medicine may derive from this fact.

In time, the list of plants that can safely be said to contain cannabimimetic compounds will no doubt expand dramatically, as we continue to find compounds capable of acting on the EC system.

But do any plants produce classical cannabinoids, other than cannabis?

Up until very recently indeed, it seemed that the cannabis plant was unique in producing the true, classic cannabinoids. However, this conventional wisdom appears to have been turned on its head with the discovery in 2012 that flax (linen) seeds produce cannabidiol (CBD)! Or at least, that they produce cannabinoid-like compounds very similar to CBD, which appear to have similar anti-inflammatory effects.

However, there is in fact a much earlier piece of research suggesting that the compound cannabigerol (CBG) and its precursor cannabigerolic acid (CBGA) are present in a South African herb, and a more recent (2011) study suggesting that cannabichromene (CBC) and some related compounds are present in Chinese rhododendron.

Lastly, there is even a plant known as the New Zealand liverwort, which produces an unusual type of cannabinoid (called perrottetinenic acid) that appears to be very closely related to THC, so much so that it may actually act on the CB1-receptor! If this is the case, it will be the only other known plant compound found in nature that is capable of doing so. However, whether or not this compound actually acts on the CB1-receptor is not yet known.

And one thing we seem to know for sure: no other plant aside from cannabis produces THC.

Author: Seshata @ Sensiseeds

Top 5 ways that cannabis can affect the menstrual cycle!

Cannabis, with its rich spectrum of phytocannabinoids such as THC and CBD, has long been used in traditional medicine relating to fertility and reproduction. Now, scientists are beginning to discover just how important the endocannabinoid system is to the biological mechanisms controlling these fundamental processes.

 

1. May reduce fertility during ovulation phase

Cannabis may help soothe painful cramps during the menstrual period (© Amy Messere)
Cannabis may help soothe painful cramps during the menstrual period (© Amy Messere)

There have been various studies conducted on the relationship between the endocannabinoid system and the female reproductive cycle. It has been repeatedly shown that levels of the crucial endocannabinoid anandamide vary drastically at various points of the menstrual cycle.

Anandamide levels appear to be at the highest at the point of ovulation—the moment that the egg is released from the ovary. As anandamide is an agonist of the cannabinoid receptors, one might expect that high levels of THC (which is also an agonist) would not necessarily be detrimental to ovulation.

However, a handful of studies from the 1970s and ‘80s suggest that THC has a strong ability to block ovulation in many mammals, including primates (although there do not appear to be any studies specifically on human females). It appears that THC does so by suppressing the production of a hormone critical to the ovulation process, known as luteinizing hormone.

As with most aspects of cannabinoid science, more research is required to establish exactly what the link between cannabis use and ovulation is. Interestingly, however, it does appear that tolerance to the ovulation-blocking effect of THC may build up in habitual users.

2. Can reduce painful cramps during menstrual period

Cannabis has been used in traditional herbal medicine in cultures throughout the world as a remedy for painful menstrual cramps. Famously, the British Queen Victoria was also said to have used cannabis to soothe her painful cramps—and given that her personal physician was the renowned cannabis doctor William B. O’Shaughnessy, that story most likely is true (and given that she knighted him some years later, she must’ve really appreciated it)!

Today, women throughout the world continue to use cannabis to soothe their painful cramps, and experience great subjective relief—yet there have been no formal studies to back up its efficacy, and the underlying biological processes at work have not been defined.

However, it is well-known that THC can act as a powerful analgesic and antinociceptive agent (analgesic is a general term for painkiller; antinociceptives specifically stop the nerves from sensing pain signals at all). As well as this, both THC and CBD have the ability to reduce inflammation, which may contribute to the subjective reduction in discomfort.

For those searching for pain relief without the psychoactive effects of THC, CBD Oilcan be an adequate solution.

3. Suppresses key hormones during premenstrual phase

THC has been observed to alter cycle length in female rhesus monkeys (© Nina A.J.)
THC has been observed to alter cycle length in female rhesus monkeys (© Nina A.J.)

During the premenstrual phase (which is also known as the luteal phase), hormonal fluctuations can cause a wide range of symptoms including pain, irritability, mood swings, fatigue, and bloating. It is well known that levels of certain hormones, including progesterone, significantly increase during this phase (while other hormones including estrogen become depleted).

For years, doctors have prescribed supplementary progesterone as a treatment for severe premenstrual syndrome, but recent research indicates that this is ineffective. Indeed, although it is generally thought that abnormal premenstrual symptoms are linked to low progesterone levels at a time when they should be high, some forms of premenstrual syndrome (the name given to the phenomenon of experiencing abnormally severe symptoms during this time) appear in fact to be linked to excessive progesterone levels and reduced estrogen levels.

Clearly, premenstrual symptoms severe enough to be classed as PMS are a result of hormonal fluctuations and imbalances. Furthermore, there is evidence to suggest that cannabis use suppresses the level of progesterone during the luteal phase, as well as altering levels of other important hormones known as prolactin and cortisol. As well as this, the inhibiting effect of THC on luteinizing hormone that begins at the time of ovulation is also observed to occur during the luteal phase (which is the window between ovulation itself and commencement of the menstrual period).

Again, while the precise mechanisms at work have not yet been fully described, it is clear that the endocannabinoid system has a role to play, and that women who experience abnormal symptoms at this time may benefit from targeted cannabinoid therapies.

Indeed, there are countless women throughout the world who experience subjective relief from cannabis during the premenstrual phase, although this may result from the known anti-anxiety and relaxant effects of cannabis more than from direct influence on hormonal levels.

4. May decrease length of menstrual cycle

Again, the evidence for THC causing a shortened menstrual cycle in human females is sparse. A 1986 study on the effect of THC on luteinizing hormone also observed overall duration of the menstrual cycles to be reduced in women given cannabis compared to those given placebo.

Thus, more research is required before it can be said with any degree of certainty how and if the duration of the menstrual cycle is affected in human females. As with the ovulation-blocking effect of THC, it may be that tolerance builds up rapidly to any possible effect.

Interestingly, older studies on nonhuman primates indicate that THC may alter cycle length, but not necessarily shorten it: on a 1980 study on rhesus monkeys, the sample treated with THC overwhelmingly exhibited significant increases in cycle duration. One monkey had a cycle length of 145 days, compared to the usual 30!

5. May affect embryo implantation in the uterus

Cannabis has also been reported to increase sexual arousal in women (© SkillingsVideo)
Cannabis has also been reported to increase sexual arousal in women (© SkillingsVideo)

There have been several important studies published over the last decade or so investigating the finely-tuned influence of the endocannabinoid system over various key processes relating to  conception and early pregnancy.

Several of these studies have found that anandamide levels fluctuate dramatically throughout the monthly cycle, and that levels are at their lowest during the “implantation window” (the brief window of time in which the embryo can successfully be implanted in the endometrium of the womb, which typically occurs last for around three days and begins six to nine days after ovulation).

In studies where anandamide has been artificially increased at this stage, implantation generally has failed to occur. Given that anandamide and THC are both agonists of the cannabinoid receptors, it would appear to make sense that consumption of THC during the implantation window could cause the same effect (however, this concept is overly simplistic, and does not necessarily hold up with such a complex system as the EC system).

However, until further research fully elucidates the association, the possibility that use of high-THC cannabis could prevent a fertilised ovum from becoming implanted in the endometrium during the implantation window means that it is highly advisable for cannabis users wishing to become pregnant to cease use of cannabis at least 24 hours prior to their “implantation window” opening.

The fact that THC appears to have the ability not only to inhibit ovulation but also prevent implantation of fertilised eggs in the endometrium suggests that there could be the potential for it or compounds like it to be used as the basis for non-hormonal birth control drugs.

Due to the fact that tolerance build-up appears to be somewhat of a problem with THC itself, there are probably better candidates out there for targeted research. After all, if consistent THC use alone were enough to prevent pregnancy, fertility rates would be drastically lower in heavy cannabis users compared to the general population, and there is no indication that this is the case!

However, there is substantial evidence that cannabis use enhances sexual pleasure in users, which could go some way towards counteracting any negative effect on fertility rates…

Author: Seshata @ Sensiseeds

Cannabis and human fertility

Use of cannabis may have various effects on human fertility, depending on gender, general health, socioeconomic status and several other factors. Here, we take a look at existing research on cannabis and human fertility, in order to provide readers with an accurate, up-to-date summary of the current state of scientific knowledge.

 

Cannabis use and male fertility

Various studies into the effect of cannabis use on male fertility have indicated that regular use may reduce spermatogenesis (the production of sperm in the testes) and testosterone levels.

In 2012, a review of research on the effects of illicit drug use on male fertility was conducted for the American Society of Andrology. The researchers found that in the majority of studies, it was consistently concluded that cannabis use had a negative impact on male reproductive physiology.

Cannabis use has been associated with poor fertility in males and females
Cannabis use has been associated with poor fertility in males and females

An early study (Kolodny et al, 1974) into testosterone levels in “chronic” cannabis users found that 6 of 17 subjects had oligospermia (low sperm count), and that average testosterone levels in the cannabis-using group were just over half that of the control group. The effect of cannabis on testosterone levels was observed to be dose-dependent.

A 1992 study (Vescovi et al.) found that levels of luteinizing hormone(LH), an important pituitary gland hormone involved in reproductive function, were reduced in male chronic cannabis users compared to a non-cannabis-using, age-matched control group. A previous 1986 study (Cone et al.) also found a significant reduction in LH levels immediately after  smoking cannabis.

The endocannabinoid system and male fertility

Clearly, the endocannabinoid system has a role to play in the regulation of processes critical to male reproductive health, such as sperm count, testosterone levels, and levels of other key hormones such as LH.

For healthy adult males, it seems that use of THC does indeed cause some negative effects on fertility, and that negative effects tend to increase with higher doses. However, THC’s endogenous analogue anandamide appears to be critical to the functioning of the male reproductive system.

It was first observed that type-I cannabinoid receptors were present in human testes in a 1993 study (Munro et al.). In 2002, a later study (Schuel et al.) observed anandamide in human seminal fluid, and CB1-receptors in human spermatozoa.

The 2002 study found that sperm cells would bind to the agonist CP-55,940, demonstrating the presence of CB1-receptors. The study also concluded that presence of THC and a synthetic anandamide analogue, AM-356, both reduced sperm motility in vitro. Interestingly, it was found that AM-356 exerted a biphasic dose-dependent effect on sperm motility, causing inhibition at high doses but hyperactivity at low doses.

Anandamide and the “capacitation” of human sperm cells

In a 1994 study (Yanagimachi, 1994) , it was found that mammalian sperm, including that of humans, is actually incapable of fertilizing oocytes (eggs) immediately after leaving the testes, and requires a period of exposure to certain crucial hormones, enzymes and proteins on its journey through the vas deferens and ejaculatory ducts of the male reproductive system (as well as the reproductive fluids of the female vagina and oviducts) before becoming “capacitated” and able to fertilize an egg.

Sperm motility is adversely affected by heavy cannabis use
Sperm motility is adversely affected by heavy cannabis use

The 2002 study provides strong evidence that the presence of the endogenous agonist anandamide in the seminal fluid, and its ability to bind to the CB1-receptors of the spermatozoa, are key to the “capacitation” of sperm cells on their way to the ejaculatory ducts when present in the appropriate concentrations, and that when levels of anandamide are too high, it can instead have a dramatic inhibitory effect on the sperm cells’ ability to fertilize oocytes.

Why is anandamide beneficial, while THC may not be?

Although THC and anandamide are both agonists of the CB1-receptors, they differ greatly in structure and therefore have different effects on certain metabolic processes. Anandamide has a much shorter half-life than THC (just a few minutes for anandamide compared to as long as 24 hours for THC); thus, while anandamide will degrade shortly after it contacts a receptor, THC can remain in nearby adipose tissue for much longer periods, and can continue to stimulate the receptors, ultimately causing overstimulation and potential negative effects.

As is so often the case with cannabinoid science, dosage is everything—and it may well prove to be the case that very small doses of THC could benefit males who have reproductive issues that can be tied in to low levels of anandamide.

Cannabis use and female fertility

While the effect of cannabis use on male fertility appears to be quite straightforward—male chronic users of cannabis are likely to experience some degree of impairment to reproductive physiology—the effect on the human female reproductive system is less clear-cut.

Female reproductive health is vastly complex in itself, as it not only comprises the ability to become pregnant but also the ability to carry healthy offspring to term and successfully give birth.

Anandamide is present in the vas deferens, where it assists in sperm capacitation
Anandamide is present in the vas deferens, where it assists in sperm capacitation

Past research has indicated that cannabis use may disrupt the menstrual cycle, suppress oogenesis (production of eggs in the ovaries) and impair embryo implantation and development. Chronic use of cannabis has also been repeatedly associated with lower birth weight, increased foetal abnormalities and early (spontaneous) termination of pregnancy.

However, most of these findings are far from conclusive. For example, a 1985 paper on foetal abnormality (Qazi et al.) after prenatal exposure to cannabis discussed five infants whose mothers acknowledged use of cannabis prior to and during pregnancy and who were born with various symptoms of growth retardation, neurological dysfunction and deformity; such a small sample size, however, is far from sufficient to draw concrete conclusions, and correlation does not imply causation.

Other studies seen as providing evidence that cannabis use can cause foetal abnormalities are animal studies (Geber & Schramm 1969Phillips et al, 1971) in which rabbits, hamsters, rats and mice were injected with vast doses of crude cannabis extract, as much as 666mg/kg in one instance! Such massive doses of cannabis would be practically impossible for a human to consume through conventional means, and are essentially useless as a point of comparison.

In fact, many early studies that indicated a correlation between use of cannabis (or other controlled substances such as cocaine) have been later contradicted by findings suggesting that socioeconomic status and level of poverty are far more causative of low birth weight and poor developmental outcome than use of the substances themselves. This does not imply that use of cannabis or other substances during pregnancy has no adverse effect, but does give weight to the idea that the risks have been overestimated and overemphasized due to politics and anti-drug bias.

The endocannabinoid system and female fertility

Just as in males, it is clear that the endocannabinoid system does have an important role to play in female fertility. CB1-receptors have been shown to be present in the ovaries, the uterine endometrium, and the developing embryo (McPartland, 1999); anandamide has been found to be present in the oviductal and follicular fluid (fluids found in the Fallopian tubes and the follicular antrum; the follicular antrum is the chamber in which ovarian follicles produce oocytes, or immature egg cells). Both CB1- and CB2-receptors have also been found at all stages of development of the oocyte itself (Taylor et al, 2010).

Anandamide is present in high levels during oogenesis and ovulation
Anandamide is present in high levels during oogenesis and ovulation

As previously mentioned, mammalian sperm cells require a period of exposure to both male and female reproductive fluids in order to become “capacitated” and able to fertilize an egg. The presence of anandamide in the female reproductive fluids thus clearly assists in the capacitation of sperm cells on their journey to the Fallopian tubes.

As well as assisting in capacitating the sperm cell and facilitating its journey to the Fallopian tubes where fertilization takes place, anandamide and the CB1-receptors have a crucial role to play in ovulation, as well as in the implantation of the fertilized gamete into the endometrium, or the lining of the womb. Specifically, it has been shown that high levels of anandamide are necessary for successful ovulation, and that lower levels are advantageous during the implantation of the gamete into the uterine lining (Talatini et al, 2009). The same study also indicated that anandamide levels are high during the 4th-5th weeks of gestation, and drop to much lower levels during the 6th week.

The concentration of anandamide in the oocytes has been found to strongly correlate with the maturation and quality of the oocytes (Taylor et al, 2010), which in turn determine the success of ovulation. It is not clear exactly by what mechanism anandamide works to control oocyte maturation; the fact that high levels of anandamide are necessary at this time would appear to contradict the findings that use of THC can disrupt oogenesis and ovulation.

The process may indeed be complicated by the role of the endocannabinoid system in digestive health: cannabinoids are known to affect key physiological processessuch as appetite and glucose metabolism, thereby potentially working to reduce the chances of obesity; obesity is strongly linked to reproductive health, so even if THC can be seen to have a negative effect on ovulation in itself, its positive effect on nutritional health may outweigh this negative effect to produce an overall positive effect on fertility.

The role of cannabis & endocannabinoids in fertility & birth control

Although it does appear that heavy use of cannabis can have a negative effect on human fertility and reproduction, the extensive research that has been done on the subject has paved the way for a far deeper understanding of human reproductive physiology, and has opened the door to the possibility of targeted, endocannabinoid-based treatments for the 10-15% of couples worldwide that suffer from poor reproductive health.

Furthermore, while use of cannabis and exogenous cannabis may in many cases be detrimental to human reproductive fitness on an individual level, they may on the other hand prove useful as a non-invasive means of controlling fertility in populations with fertility rates well above the rate of replacement (the rate at which new babies must be born to replace individuals that die, in order to maintain the overall size of a population).

A deeper understanding of the endocannabinoid system's effect on fertility will enable us to develop targeted therapies
A deeper understanding of the endocannabinoid system’s effect on fertility will enable us to develop targeted therapies

Ultimately, to gain a clear perspective on the extent to which cannabis use truly affects overall fertility in the sense of number of children per fertile female, we should look at the numbers of children born to cannabis users compared to non-users. However, there are various other factors that may affect number of children born, including level of education, socioeconomic status and overall desire to reproduce.

Thus, it is far from clear what overall effect higher rates of cannabis use will have on fertility rates in different populations. But as we struggle to prevent our global population from increasing to unsustainable levels, clamping down on the (very widespread) use of a substance that may reduce rates of fertility in a given population could prove to be highly disadvantageous long-term strategy.

Author: Seshata @ Sensiseeds

10 things you did not know about cannabis

You probably know a lot about cannabis. In fact, these days if you don’t have a basic knowledge of cannabis you probably don’t pay much attention to current affairs, given how much focus the media has paid to it in recent years. Still, there’s always more to know, so we’ve compiled a list of our favourite little-known facts!

Cannabis is the world’s most valuable crop

This fact is by no means obscure, but it is surprising how few people understand the true, unbelievably huge value of the global cannabis crop. Not only is it the world’s biggest cash crop in absolute terms, with a gross production value of over $300 billion in 2014, it is also the most lucrative per square kilometre–at $47.7 million/km², it far outranks its closest competitor cocaine, which brings in an impressive $37.7 million/km². And it does so on just a fraction of the land used to grow rice, maize, and wheat, the highest-grossing conventional crops. These three crops each take up around 2 million km² in land, while cannabis was estimated in 2010 to take up just 6,148 km²!

In Bhutan,  cannabis is used as pig feed

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In Bhutan, cannabis is so abundant that it is fed to pigs (© nutmeg66)

In the Himalayan Kingdom of Bhutan, wild cannabis grows so prolifically that the locals view it as a nuisance and even feed it to their pigs. The tiny, landlocked kingdom has historically been highly insular and strictly Buddhist–and not the kind of Buddhist that approves of intoxication! Thus, having no culture of cannabis use as an intoxicant, the Bhutanese have traditionally had very little use for it. However, in recent years as television (and foreign media) has infiltrated the country, there are increasing signs that the country’s youth are wising up to the possible pleasures of their wild bounty.

Japanese ninjas once trained by leaping over hemp plants

In this fascinating article, one of Japan’s leading experts on cannabis, Junichi Takayasu relates how a childhood book inspired him to grow cannabis (and how displeased his mother was when she learned of his ambition!); this book illustrated how ninjas-in-training would start a crop of hemp, and each day as it grew rapidly taller would be forced to leap higher and higher over it, and thus develop their leg muscles. Takayasu was so inspired that he now runs Japan’s only museum dedicated to cannabis and hemp!

The Bashilenge was a cannabis cult in 19th-century Congo

In 1881-1882, the German explorers Pogge and Wissman travelled throughout the southern Congo basin, and in the course of their journey they encountered a sect of hemp-worshippers known as the Bashilenge, who also called themselves Bena-Riamba, meaning “sons of hemp”. They cultivated vast fields of cannabis, the harvestof which featured heavily in all manner of important rituals, such as business deals, holidays, and peace treaties. Members of the cult were required to show their devotion by smoking as much cannabis as possible, and the hemp pipe took on a significance similar to the peace pipe of the Native Americans!

In England, hemp ropes were used by professional hangmen

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In England, hangmen’s nooses were made from hemp (© Theglobalpanorama)

Before capital punishment was made illegal in England in 1965, professional hangmen used hempen ropes as nooses, due to their superior strength and relative lack of elasticity. Hemp was the preferred material, but would often be mixed with other fibres such as Italian silk, to make the drop smoother. Use of hemp ropes by hangmen became so ingrained that a noose was often referred to as a “hempen necktie” or just “a hemp”.

In Switzerland, cannabis was once sold in “aromatic pillows”

At the height of Switzerland’s famously relaxed drug policies at the turn of the 21stcentury, hundreds of cannabis shops throughout the country sold small amounts of cannabis packaged as “aromatic pillows” or “bath scents”, on the proviso that they were not for human consumption. Unfortunately, the laws subsequently tightened up and the aromatic pillows are no longer available–although the laws relaxed yet again in 2013, and Geneva and several other cities are now thinking about permitting retail sales of cannabis.

Hemp has been used to make bulletproof clothing

Hemp fibre truly is a wonderful thing. It has clothed humanity for thousands of years, and in modern times has been used in countless innovative new ways. One of the most astonishing of these new applications is in the manufacture of high-strength fabrics, some of which are strong enough to stop a 22-calibre or even a 9mm bullet. Clothing designer Hemp Hoodlamb has a IIA-rated bulletproof coat, the HHL Classic Bulletproof, which has been tested to stop a .22 and a Glock 9mm!

In Iran, they have been making cannabis extracts for hundreds of years

In Europe and North America, cannabis concentrates such as wax and shatter are really just starting to explode in popularity, although the basic techniques have been in use for thirty years or more. However, our expertise pales in comparison with that of traditional Iranian hash-makers, who worked out a method of adding ground-up weed to near-boiling water to extract the resin, which they called row?an-e bang. When the cannabinoid-rich oils are heated by the water, they rise to the top of the container while the plant matter sinks. The oily globules can then be skimmed off and dried, producing a basic yet highly effective form of pure cannabis oil!

Cannabis was widely used in 19th-century American veterinary medicine

It’s widely-known that cannabis has a long history of use in medicine, but what is less well known is that it’s not just humans that we traditionally treated with cannabis, it was our livestock too. Historic texts from various countries attest to cannabis used in veterinary medicine, but it is arguably the USA that had the most developed pharmacopoeia of cannabis-based animal medicine. Look here for a gallery of dozens of tinctures and ointments used to treat all manner of maladies in horses, cows, sheep and various other farmyard beasts.

Ancient Europeans held erotic, naked rituals in honour of hemp

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In ancient Europe, naked fertility rites were carried out in the hemp fields (© Edward the Bonobo)

Throughout much of ancient Central and Northern Europe, the Nordic goddess Freyja was worshipped as a deity of love and sexuality. She was also associated with hemp, and during the sowing and harvesting of the yearly crop some remarkably salacious fertility rituals took place, involving “marriageable boys” and female participants that were “required to be totally or partially naked“. The source provided also goes into some interesting detail about Catholic girls going in groups into the hemp fields and rolling around naked among the plants… Anyway, it seems that these peculiar customs have tragically died out, more’s the pity.

Author: Seshata @ Sensiseeds

 

What are the differences between hemp oil and CBD oil?

The range of cannabis or hemp-based products available to the public is increasing over time. Variety is most welcome, as each of these products caters for different needs. Hempseed oil, cannabis oil, CBD oil … there are many options, that can be confusing to the average consumer. In this article, we break down the differences between hemp oil, also known as hempseed oil, and CBD oil.

Hempseed oil 101

Hempseed oil is, as its name indicates, extracted from pressing hemp seeds. Hemp seeds are not psychoactive (4mg of THC/kg) upon consumption of any kind. Hemp oil is legal in most countries, and can be found in food markets, together with other types of oil.

CBD oil 101

CBD oil is obtained via extraction made from cannabis flowers, preferably of a cannabis and hemp strains extremely rich in CBD (cannabidiol)Proper CBD oil can only be found in places where it has specifically been made legal.

Medicinal properties

Sensi Seeds BlogBoth CBD oil and hempseed oil share the particularity of not being psychoactive, a fact that plays a major part in their respective popularity. Especially in a context where cannabis is not legal in all countries, it makes for a safer alternative, as opposed to consuming cannabis. It also allows underage consumption for medical reasons.

Hempseed oil

Refined hempseed oil is generally considered a food item, thus making it legal in most countries. It is known for its countless health benefits, making it part of the very sought-after group of superfoods.

  • Rich in proteins
  • Full of polyunsaturated fatty acids, such as omega 6 and omega 3
  • Vitamin E antioxidants
  • Linoleic acid (affects aging/skin conditions)

It is to be noted that hempseed oil contains some CBD. However, such small concentration would only affect positively patients suffering from non-severe to mild conditions.

Read more about hempseed oil’s benefits here.

CBD oil

CBD oil is made from cannabis flowers, from which resin and CBD are extracted, via an array of different available methods. It is recommended to seek information about the method used, and general quality of the product before acquiring CBD oil produced by a third party. Listing all the medicinal properties of CBD oil remains difficult to this day, as scientific research as well as anecdotal evidence keep uncovering more of them over time.

Read our comprehensive article covering CBD oil’s medicinal properties here.

Appearance

Sensi Seeds Blog

Visible differences between hempseed oil and CBD oil may depend on the quality of either of them. Indeed, refined hempseed oil as well as CBD oil can appear to be of a lighter or darker colour, depending on quality, age, method of preservation, etc. These two types of oil are extracted from the same polymorphic species, which explains why they look identical in most cases.
Both show a rich, golden-green colour, not unlike olive oil.

Name

Hemp oil is known under different names: hempseed oil, hemp oil, culinary hemp oil, and at times, cannabis oil. While ‘hempseed oil’ is by far the most self-explanatory of all, it is also the most accurate. In order to determine if a product called ‘hemp oil’ or any of the aforementioned terms is in fact, hempseed oil, consult the list of ingredients. While various marketing and packaging reasons may justify the use of an erroneous or vaguer term in place of ‘hempseed oil,’ the ingredients should clear this up.

CBD oil, on the other hand, is almost unmistakable for another product, as far as names go. In the majority of cases, the name ‘CBD oil’ will be used in the product’s description, or on its packaging. In rare occurrences, the words ‘cannabis oil’ are displayed; however, CBD being a staple of the medicinal cannabis industry, not mentioning the presence of it in a product would be counterproductive to say the least. Thus, it is likely a mention of it adorns some other corner of the package.

Author: Silent Jay @ Sensiseeds