2017 could be the year of the medical cannabis gold rush. While in the US almost a quarter of the country can now access the plant for medical use, Germany has made it available through the public healthcare system, and even Ireland has voted in its favour.

The plant’s two main players, THC and CBD, tend to hog both the headlines and the research grants, but there’s also a race to explore some of the other lesser known compounds in the plant, with two in particular showing promise.

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Tetrahydrocannabinolic acid (THCA) and Tetrahydrocannabivarin (THCV) may look similar in name to the psychoactive cannabinoid THC, but as more research is carried out, scientists are discovering they offer quite different therapeutic possibilities.

THCA – the raw cannabinoid

THCA is the acidic precursor of THC. If you took some some fresh cannabis leaves they would be abundant in THCA and you’d be hard pressed to find any THC itself. That’s because in order to convert THCA into THC, it must go through the decarboxylation process, i.e. exposure to heat or sunlight. And only then does it become psychoactive.

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But this raw cannabinoid does have its own therapeutic potential.

In a study carried out on rodents and published in the British Journal of Pharmacology, THCA was found to show “promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.”

In certain countries medical cannabis containing high THC is prescribed to cancer patients going through chemo to help them cope with the debilitating nausea. However, many find the additional psychoactive side effects undesirable. In these instances, THCA could provide an easier to bear alternative.

Research also suggests THCA shows promise for reducing pain and inflammation, as well as being anti-proliferative (stops cells from spreading) and is anti-spasmodic.

There are certainly many anecdotal reports of people who say they have gained great therapeutic benefit from juicing raw cannabis leaves, such as Katie Marsh who claims to be in remission from her rheumatoid arthritis thanks to this method. Could it be in part down to the high levels of THCA she was imbibing?

So what about THCV?

Tetrahydrocannabivarin (THCV) unlike THC and CBD, does not begin life as cannabigerolic acid (CBGA). Instead, it comes from cannabigerovarin acid (CBGVA). According to Wikipedia, “once CBGVA is created, the process continues exactly same as it would for THC. CBGVA is broken down to tetrahydrocannabivarin carboxylic acid (THCVA) by the THCV synthase. At that point, THCVA can be decarboxylated with heat or UV light to create THCV.”

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Despite being decarboxylated, THCV is not psychoactive. In a small study in which THCV was administered alongside a placebo and then in conjunction with THC, participants found no difference between the placebo in terms of psychoactivity and “nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense.” Suggesting that like CBD, THCV can reduce the psychoactive effects of THC.

This lack of psychoactivity is most likely due to the fact at low doses THCV does not activate the CB1 cannabinoid receptor, but actually blocks it. However, at high doses, it becomes a CB1 agonist, much like THC.

THCV – shows promise for treating epilepsy

Since the earliest written records for the medical use of cannabis, the plant’s efficacy in reducing seizures in epileptic conditions has been well documented. These days some of the most headline grabbing anecdotal stories and cannabinoid research have been about the non-psychoactive cannabinoid CBD (Cannabidiol) and its effect on children with drug resistant epileptic conditions such as Dravet Syndrome and Lennox-Gastaut.

But preclinical research suggests that THCV may also have anti-epileptic qualities with a study concluding that “Δ⁹-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.”

GW Pharma runs clinical trials on THCV and epilepsy

And a stage 1 clinical trial has been conducted by British cannabis-focused biopharmaceutical company, GW Pharma in which THCV “was well tolerated even at the highest tested dose. There were no serious or severe adverse events, nor any withdrawals due to adverse events.” A stage 2 trial is currently underway with the company stating that THCV “has the potential for development in the field of pediatric epilepsy as well as the broader epilepsy market.”

In fact GW Pharma is at the forefront of current research into the therapeutic potential of THCV. It has completed a stage two clinical trial into the use CBD and THCV for Type II Diabetes, is planning clinical trials using the cannabinoid for autism spectrum disorders, and according to its year end report for 2016, has been awarded “Orphan Drug Designation from FDA for CBDV for the treatment of Rett syndrome.”

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Could THCV slow onset of Parkinson’s?

Another reason that THCV is creating such excitement is its role as a CB2 receptor agonist, most likely giving rise to its anti-inflammatory nature and potential as an antioxidant.

In fact it is this ability to inhibit the CB1 receptor while activating the CB2 receptor that makes its therapeutic potential particularly exciting in neurodegenerative diseases like Parkinson’s.

In a paper entitled ‘Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ⁹-THCV in animal models of Parkinson’s disease,’ published in the British Journal of Pharmacology it concluded, “given its antioxidant properties and its ability to activate CB(2) but to block CB(1) receptors, Δ(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.”

And finally, in contrast to THC which is often prescribed to augment appetite, THCV has been found to be an appetite suppressant and shows potential to combat obesity and metabolic disorders. Again GW Pharma lead the research stating, “in pre-clinical studies, THCV has shown effects on body weight, body fat content, energy expenditure, food intake, and other obesity-related parameters.”

Are THCA and THCV legal?

Both THCA and THCV are not classified by the United NationsConvention on Psychotropic Substances, nor are they scheduled at federal level in the United States. But with their status as THC analogs, sale or possession could potentially be prosecuted under the Federal Analogue Act, in which any chemical ‘substantially similar’ to a controlled substance would be treated as if it were also listed in the schedules.

As ever, it’s a grey area. Certainly with THCA there is always a risk that it will contain some traces of THC, as with the ageing process of the harvested plant, so begins the chemical change from THCA to THC, and with it the possibility of prosecution for possession of a controlled substance.

But despite the legal ambiguity, it looks like THC and CBD are not going to be the only cannabinoids talked about in 2017, as THCA and THCV feature in more research and clinical trials. This combined with their non-psychoactive status, makes them of great interest for both patient and medical cannabis companies alike.

 

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