Some Comments On Marijuana 
Posted by Carlos on Dec 15, 2016

The recent elections in the United States is bringing many long-standing policies into question. And, the continued legalization of marijuana is one of them. 

At Lacerta Bio, we have consistently held the opinion that marijuana has many potential medical benefits, and that laws need to change in order to provide legitimate patient access to this plant. 

We do not believe  it is government’s role to dictate what plant a person can grow in their own home for medicinal purposes, especially in a nation where alcohol and tobacco products are readily available. 

Marijuana is no longer limited to slackers, pot heads, and concert goers. Today, the skills and techniques of synthetic biology and bioengineering are being applied to marijuana, resulting in plants with different properties.

This approach may result in tremendous benefits for patients, as well as help control the emergence of plant material with harmful contaminants. 

An entirely new industry is emerging right before our eyes, especially in the recreational side of the market. But increased access to high quality recreational marijuana may have tremendous positive benefits for many patients. 

Therefore, now seems like an opportune time to review the status of marijuana in the US, with an emphasis on medicinal uses. 

Legitimate Medical Uses

The pharmacology behind the medicinal use of marijuana is a major subject and well beyond the scope of this article. Readers are encouraged to examine reviews by Borgelt and Starowicz. Their use as antitumor agents is well reviewed by Velasco, et al. This presentation has some interesting Preclinical and Clinical data. 

The medicinal properties of the plant have been recognized for eons. As far back as 2500 BC, marijuana was recognized as having both medicinal and pleasurable properties. The US Pharmacopeia first included marijuana in 1837, but it was not removed until 1942, even though it was criminalized in 1937. 

Over the years, three markets have developed for marijuana. The first, is the recreational market. This will not be discussed in detail here, although the liberalization of laws permitting recreational use also means increased access to patients who need to use marijuana to treat disease.

The other two markets: plant material for medicinal use and synthetic cannabinoids, are discussed below. 

*~*~*~*~*

Marijuana is unique in that it has two general classes of products, and hence two distinct markets. The first consists of products made and sold in the form of the plant for delivery via smoking/inhalation. The second is the more familiar route, in which specific compounds are identified and extracted from the plant for traditional IND/NCE drug development. 

Some analysts estimate that the market for marijuana (both recreational and medicinal) is over $5 billion, and is expected to grow very rapidly. This is likely to be a gross underestimate, as many former street corner vendors have moved their businesses online, leveraging social media to grow their semi-legitimate businesses

As of November, 2016, there are 7 states were purchases of recreational marijuana is legal. An additional 18 states allow marijuana sales for medicinal purposes. But in some of these medical marijuana states, such as New York, only tinctures are permitted, not plant material. 

Smoking Pot For Health

The internet is full of pseudoscientific claims of the medical benefits of smoking marijuana. However, some of these claims are legitimate, in the sense that they are supported by some (albeit limited) preclinical or clinical data. A few examples include:

Glaucoma – It was observed in the 1970s that smoking marijuana does indeed reduce the intraocular pressure associated with glaucoma. Current thinking is that his benefit comes from the plant’s ability to lower systemic blood pressure, resulting in lower blood flow to the optic nerve, which is already an issue in glaucoma. Today, it is rare to find an ophthalmologist who will recommend or condone marijuana for glaucoma. 

Epilepsy / Seizure Disorders – The anticonvulsant properties of cannabinoid compounds have been demonstrated in a number of animal models. However, it is likely that the doses available in inhaled marijuana smoke are too low to provide a therapeutic benefit. A recent documentary suggested marijuana is effective in Dravet’s Syndrome, a form of pediatric epilepsy in which hundreds of seizures per week can occur.  Several NCEs are now being studied in epilepsy.

Spasticity – A 30-patient study concluded “Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity.” Marijuana may provide symptomatic relief in other related conditions, such as respiratory myoclonus. Patients with other involuntary movement disorders, may also benefit from smoking marijuana. 

Crohn’s Disease & Ulcerative Colitis –  A number of studies have demonstrated that cannabinoid receptors are upregulated in inflammatory conditions in the GI tract. So cannabinoids may have anti-inflammatory effects in Crohn’s or UC. Indeed, a 21-subject study demonstrated clinical benefits in 10 out of 11 patients with active Crohn’s disease. But it is unclear if the benefit is better in one disease or another, nor is it clear if the dose from smoking is sufficient. 

Considering that so many of our “modern” drugs originally started as compounds extracted or derived from plants, it should not surprise anyone that a plant with such a complex chemistry could have pharmacologic benefits. THC is but one of nearly 500 known compounds in the plant. Who knows what other therapeutic benefits can be derived from smoking marijuana? 

 

Not Without Risks

As marijuana use increases, so does the concerns (real or perceived) surrounding side effects. Some warnings are silly, i.e., driving under the influence can cause vehicular mishaps and fatalities. Substance abuse is another obvious and legitimate concern.

Weight gain and many other side effects are now being attributed to recreational use. But most of these data are anecdotal. 

Interestingly, the US is not the only country expanding access to marijuana while expressing concerns over side effects. Germany, for example, became the latest country to approve marijuana for medicinal use.

Drugs from Marijuana

Compounds derived from cannabinoids, such as dronabinol and nabilone, have been available since the mid-1980s for chemotherapy-induced nausea and vomiting. The additional indication of AIDS-associated weight loss due to anorexia was added in the 1990s.

According to MedTrack, there are 128 cannabinoid receptor (1 or 2) agonists or antagonists in various stages of development, of which 64% are in Research or Preclinical stages of development. Phase III compounds are limited to cannabidiol, dexanabinol, and dronabinol. 

Approximately 60% of the compounds under investigation are synthetic. For example, ajulemic acid is a synthetic cannabinoid which is no longer in development. But at one time, it was being investigated for post-herpetic neuralgia, skin inflammation, and other indications. In fact, synthetic cannabinoids have been in the news, but for the wrong reasons.  

The leader in this field is GW Pharmaceuticals, with one product (Sativex) approved for the treatment of multiple sclerosis spasticity. Another product (Epidiolex) is being studied in a number of Phase III programs.

 

 

Marijuana, Meet Genomics

The genome of Cannabis sativa was first published in 2011. Since then, a number of companies have emerged in order to apply their genomics capabilities to create new breeds of marijuana with different properties, such as greater potency and different aromas. Others are looking towards genomics to help improve the safety and quality of cannabis, without losing the health benefits. US-based companies in this space include Medicinal GenomicsPotBiotics, and Verda Bio

Unfortunately, as long as the FDA and DEA maintain their stance, it is unlikely that serious research will occur in the academic setting. Colorado appears to be leading the way, thanks to their Cannabis Genomic Research Initiative

Marijuana is already an estimated $20+ billion market. Source: Marijuana.com

Where Do We Go From Here?

Over the past 80 years, marijuana has gone from criminalization to therapeutic. Now we find ourselves in a world where criminal possession and genomic manipulation of Cannabis coexist. 

In our view, the time has come for states to continue their liberalization of marijuana. Given that it is already a $50+ billion market, states will likely continue to liberalize marijuana as a source of sales taxes.

To do this, several things need to happen:

Quality Control – Efforts to analyze and ensure product quality would reduce “zombie” attacks associated with plant materials of unknown origin.  

More Research – In 2015, the NIH supported 281 projects in cannabidiol research, spending $111 million in the process. This is very good, and we hope this research continues to be well-funded. However, 173 out of the 281 projects were funded by the National Institute on Drug Abuse.

While drug abuse research is undoubtably important, a greater emphasis on therapeutics, coupled with greater quality control, would be terrific. Positive results could be a steppingstone towards the identification of individual compounds (or combinations) with unanticipated therapeutic benefits in oncology, neurology, and other therapeutic areas. 

Support Liberalization – The pharmaceutical industry will not get involved in continued liberalization of plant-based marijuana products. Therefore, it is up to us as citizens to educate and support lawmakers who support liberalization for increased access to safe marijuana for legitimate medical purposes. Change will likely be very slow in many states. 

Update

Earlier this week, Massachusetts became the first state on the East Coast to legalize marijuana growth and possession for recreational purposes. Therefore, patients in Massachusetts who want to use marijuana for legitimate purposes will be able to grow their own material. That’s great news. 

Other countries are also reexamining their stance on marijuana. Germany, for example, recently legalized cannabis prescriptions.

Acknowledgement

We would like to thank Karl Schmieder from MessagingLAB for a recent insightful discussion on the subject of plant genomics.  

Disclaimer: We at Lacerta Bio do not in any way advocate the illegal purchase or use of marijuana or any other drug substance. Please always obey local and Federal laws.

Google Plus   Facebook   Twitter
Powered By : Supra International Inc.