The Illegal Nuerotransmitter: Will Spice and related products be regulated or join the street pharmacoepia?

Sunday, September 19th, 2010

Due to concerns over the use of Spice and similar herbal products sprayed with cannabinoids, government officials have been advising that these substances become controlled drugs. The United States has become concerned with this issue…so much so that even I was recently contacted by the Dr. Phil show for information on ‘Spice’ or “K2″. The current Dr. Phil episode was centered around the issue of the safety of these drugs. With limited scientific information  fear and fantasy have started to run rampant, overshadowing other important issues surrounding this synthetic phenomena. There is a lot to discuss and learn about these popular drugs, as other countries are starting to deal with the issue. However, there are no studies on the prevalence of use and we are just starting to understand why people are using this stuff.

Here are some links to background info on ‘Spice’:

1) Facts about new synthetic drugs K2 or Spice

2)Spice prohibition is short sighted

3) Truth about K2 and Spice

The UK attempted to deal with the problem but it was soon realized that the reality of the situation would not yield a politically palatable solution. As the scientific community, at least in the UK,  basically suggested regulating these herbal preparation or legalizing cannabis would be the responsible thing todo. Let’s review some of this global discussion and we may see what happens when science and politics collide.

To set the stage for the discussion we should start in late 2009 in the UK. The Gordon Brown government had began to reschedule cannabis from a less harmful drug to a more harmful drug, carrying with it immense penalties for use. While this anti-cannabis legislation was being worked out, Spice use seemingly appeared and took off quickly. The reclassification of cannabis may have given the synthetic cannabis industry a push. The government then moved  to criminalize all cannabinoids, including natural and synthetic compounds. Scientists began to speak out but the discussion quickly ended when the Chairman of the Advisory Council on the Misuse of drugs, Professor Nutt “was sacked after he said that cannabis is less harmful than nicotine or alcohol and there was no evidence to back the government’s decision to reclassify the drug. “It seems unlikely that any ‘true’ scientist — one who can only speak the truth — will be able to work for this, or future, home secretaries,” Nutt wrote in the Times. The firing of Dr.Nutt sent a message to medical and scientific advisers, that science must fit the governments views or prejudice on the issue. Since then only a handful of scientists have dared published their opinions in scientific and medical journals such as the Lancet and Addiction.

Here is a link to an article on Cannabis by Dr.Nutt : Guardian UK

More links to News Article on UK’s Cannabis reclassification:

1) BBC Science chief backs Cannabis view

2) Nutt vows to setup new Drug body

3)Gordon Brown: I am right to overrule drug advisers

As discussions of cannabis and cannabinoid regulations continue, more and more prominent scientists are speaking out. Recently a renowned cannabinoid researcher spoke out at a UK science festival. Here’s an exert from the IACM bulletin and links to News Articles:

“Professor Pertwee, who is an eminent expert on cannabis and
cannabinoids for 40 years, is a former President of the
International Cannabinoid Research Society and a former
Chairman of the International Association for Cannabinoid
Medicines. He says that a group should be set up with expert
pharmacologists, lawyers and police, amongst others, to thrash out
the issue. He wants the “social, ethical, legal and economic
factors in addition to current medical and pharmacological” factors
to be taken into account: “We need a better solution than we have
now.” “You need to avoid younger people taking it: perhaps have
a minimum age of 21. You might have to have it licensed so that
you can only take it if it’s considered medically safe for you to do
so. We have car licences, so why not cannabis licences?” he said.”

British Science Association article on Dr.Pertwee

UK Guardian Article on Rogert PertWee

As these herbal mixtures are explored they appear to be a complex mixture of synthetic and natural compounds. A team in Japan found 7 sources of these herbal designer drugs contained Oleamide. A generic ban on spice products could lead to banning an endogenous cannabinoid that humans and animals make. It appears to be important for regulating sleep and is being developed as a therapeutic agent. Synthetic variations of Oleamide appear to have anti-cancer activity. If such generic bans continue, Will Oleamide then become the “illegal neurotransmitter?”

In the journal of Addiction Richard Hammersley discusses the dangers of banning spice and related compounds. Hammersley discusses the origin of the politics around synthetic cannabinoids. As Hammersley says a” generic ban may not make criminological sense, and there is a risk that it will make this herbal market more dangerous.”

In online discussions and retailer’s websites, the effects of these herbal preparations are said to mimic cannabis (cannabimimetic). If a ban were to take effect, Hammersley points out, it would turn the users to an illegal market, which would inevitably harm otherwise law abiding citizens, who have chosen not to be involved with an illegal market. These herbal products also pose a difficult problem for law enforcement to identify as these compounds do not have a characteristic appearance or smell. Furthermore, Hammersley also asks,  “what other legal products have ever been banned without industry consultation?” This is a unique opportunity to handle ‘herbal highs’ in a responsible manner; rather than give control of their strength, purity, and safety to criminal elements.

Hammerlsey goes on to argue that there is a clear demand for legal ‘highs’ and this may continue to be supplied by other cannabinoids that are not yet banned. The manufactures may have tried to produce a relatively safe product with the desired effect. Perhaps their own market research or self-experimentation has excluded chemicals that have obvious bad effects. Interestingly, some samples contain high levels Vitamin E; perhaps it’s added for it’s antioxidant properties?

Following a ban, these drugs may be replaced with others, leading to the use of truly dangerous ‘highs.’  Without further research there is a serious risk of banning a relatively less dangerous class of chemicals, which will be replaced by more dangerous ones.

In the Lancet, two letters were published regarding the reclassification of synthetic cannabinoids ( 1 & 2). The authors disagree that synthetic cannabinoids “do not have a recognized medical value.” For instance, Nabilone ( a synthetic derivative of THC) is available by prescription in the United States. Originally, these synthetic cannabinoids were developed as therapeutic derivatives of the cannabis plant. The medical use of cannabis and its derivatives has been described in the scientific literature, as well as in the U.S. governments I.O.M. report, and “British Medical Association book Therapeutic Uses of Cannabis.”

They also are concerned that a ban would severely inhibit our ability to respond effectively to potential adverse health effects. Our hospitals have virtually no information that can be used to base advice, provide information, and interventions.

We need more information from laboratory work and cross sectional studies, as there is virtually no medical information on prevalence of use and adverse effects.  Presently, the media relies on self-experimentation reports and websites of Internet retailers. The necessary information is unlikely to be forthcoming following a change in the legal status of synthetic cannabinoids.


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Scientists Find New Sources of Plant Cannabinoids

Monday, July 12th, 2010

The British Journal of Pharmacology (link to article: BJP) has devoted another issue to the theme of cannabinoids. This issue contains numerous intriguing articles that you would be hard pressed to find discussed among media and science outlets.  In a recent NPR Science Friday show on medical cannabis, Ira Flatow and guests suggested that there is a suppression of cannabis and cannabinoid research findings due to politics. This causes some journals to reject cannabinoid research without even reading the manuscript.  Research journals are hesitant to publish research on cannabinoids, and many researchers often have to squander valuable funds re-submitting articles until they find a journal that will allow their research to be peer reviewed.  The BJP deserves our attention for the great service it is doing for cannabinoid researchers—allowing our findings to be shared and discussed. One particular article in the BJP captured the imagination and wonder of cannabinoid science. The authors speculate on additional sources of plant cannabinoids, beyond the cannabis plant.

It appears that other plants produce things that directly and indirectly affect the Endocannabinoid system (ECS). The ECS is a system in our body which produces compounds or ligands that activate specific receptors. This system regulates important functions of mammals. If you have ever slept, eaten, forgot, or relaxed then you have used your ECS.

The receptors for cannabinoids are one of the most abundant receptors in the human brain and are expressed in nearly every tissue and cell. The two main receptors are the CB1 and CB2 receptor. CB1 is located in the brain and on neurons throughout the body, while the CB2 is mostly found in the immune system. Given the abundance of these receptors, it’s not hard to imagine that these receptors are important for something.   However, THC and other cannabis parts are not the only plant compounds which can affect the ECS. Other plants produce compounds which can change the production and breakdown of Anandamide. Anandamide activates the same receptor as THC and is one of many endogenous cannabinoids produced by our body.

The recent discovery of different plants with compounds that can modulate this system means we can no longer simply define plant cannabinoids as merely a product of cannabis. The authors propose that the term phytocannabinoid is more appropriate now that scientists have discovered that Beta-Caryophyllene activates the CB2 receptor and is “among the most abundant plant essential oil component.” Beta-caryophyllene in found in nearly all plants, in fact it was proposed years ago that it is a “dietary cannabinoid.”

So, what else have you been eating that mimics the effects of molecules from cannabis?

Echinacea, Ruta graveolens (Citrus Family), and the Brassica genus (Mustard family, i.e. Broccoli) all contain compounds which may bind the CB2 receptor, some with an affinity or strength similar to THC. Note that unlike the CB1 receptor, the CB2 receptor does not cause psychotropic effects.

Even the Apiaceae family contains a compound which interacts with the CB1 receptor.  Why should you care about the Apiacea family? Carrots.

Carrots and its relatives contain the compound falcarinol.  This appears to interact with both cannabinoid receptors, undergoing a mysterious alkylation reaction at the CB1 receptor. The questions of how and what this compound is doing to the CB1 receptor still needs to be investigated before we can draw any conclusions about the similarities between cannabis and carrots.

Polyphenols are common components of tea and were speculated to interact with cannabinoid receptors. However, according to this article, Gertsch and collegues think that these may be non-specific interactions.  The smelly molecular class of compounds known as terpenoids represents another potential group that can modulate the effects of cannabis and may affect the ECS. Terpenoids are abundant in vegetables and fruit.

One misconception or urban legend regarding cannabis is the presence of cannabinoids in chocolate. Sorry to disappoint some of you but that infamous research has never been duplicated… However what is true about chocolate and cannabinoids is far more fascinating and beautifully complex.  There are fatty acid derivatives in chocolate and many other plants which inhibit the FAAH enzyme. The FAAH enzyme destroys or eats Anandamide. The blocking of this FAAH enzyme leads to an increase or elevation of the levels of Anandamide. That’s right chocolate, like aspirin, elevates the so called “natural THC” in your body. No wonder chocolate is so popular. Halloween will never be the same for this scientist.

It is obvious that phytocannabinoids are found in abundance in nature, is our next step to regulate these plants like cannabis, since large doses of the active ingredients may have some cannabis-like effects?  Maybe less drastic actions should be taken.

A lot of work remains for scientists to determine the effectiveness of these phytocannabinoids and related compounds.  If you want to engage in cannabis research, a great place to start would be looking at other ingredients of a healthy diet for new members of the phytocannabinoid family.

Nature has provided a single plant which produces THC-acid. THC-acid readily becomes THC, the most potent phytocannabinoid known to man. Why does nature not provide a single other plant that produces this compound? When all around us, we can find molecular messengers from plants that influence subtle components of the endcannabinoid system.

The take home message is that fatty acid derivatives, terpenes, and polyphenols are found in numerous plants. Fruits and veggies represent another source, if not treasure troves, of compounds which may interact with the endocannabinoid system.

I don’t know about you but I am certainly looking forward to having my next snack; maybe some fruit, a cup of tea, and just a few bites of chocolate.

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