What is Tetrahydrocannabivarin (THCv)? No Longer a Minor Cannabinoid

by | Apr 8, 2024

Written by Jessica McKeil

Jessica McKeil is a cannabis writer and B2B content marketer living in British Columbia, Canada. Her focus on cannabis tech, scientific breakthroughs, and extraction has led to bylines with Cannabis & Tech Today, Terpenes and Testing, Analytical Cannabis, and Grow Mag among others. She is the owner and lead-writer of Sea to Sky Content, which provides content and strategy to the industry’s biggest brands.

Tetrahydrocannabivarin (THCv) is a cannabinoid produced naturally by cannabis plants. But it’s also popping up as a THC alternative in hemp-derived consumer products. At a molecular level, THCv is similar to THC, but it produces noticeably different effects — far milder and less psychoactive ones.

Over the last decade, THCv has gone viral as the so-called ‘diet weed’ due to its possible appetite-suppressant effects. This is just one unique interaction with the body’s endocannabinoid system, and there are now other (and more substantiated) therapeutic applications on the books.

Focusing on the science, effects, and strain development of THCv, we explore the implications of this fascinating cannabinoid from both medical research and recreational perspectives.

What is THCv?

  • Molecular weight: 286.41 g/mol
  • Boiling point: 220ºC

Tetrahydrocannabivarin (THCv) is a naturally occurring cannabinoid produced by the species cannabis sativa L. Structurally, THCv is very similar to tetrahydrocannabinol (THC), the primary psychoactive compound found in cannabis, but it is non-intoxicating. It has a propyl (3-carbon) side chain instead of a pentyl (5-carbon) side chain, making it less psychoactive than THC.  

The first recorded study of THCv was by Roger Adams and his colleagues in 1942, in their paper “Tetrahydrocannabinol Homologs and Analogs with Marihuana Activity.”

THCv molecular structure

THCv and the Endocannabinoid System

THCv has a slightly different relationship with endocannabinoid receptors compared with its THC cousin. According to Amos Abioye, Oladapo Ayodele, et al., who published in the Journal of Cannabinoid Research in 2020, “Unlike THC, which is psychoactive and an agonist at the CB1 and CB2 receptors, THCv is a non-psychoactive, neutral CB1 antagonist / reverse agonist and may act as agonist or antagonist at the CB2 receptors depending on its dose.”

Because of this unique relationship and interaction with the CB2 receptors, the working hypothesis is that THCv could reduce or mitigate the psychological effects of THC, but this specific mechanism isn’t yet understood.

THCv vs. THC

THCv vs THC are molecularly similar, yet the structural difference leads to crucial differences in effects

In one recent placebo-controlled study, researchers detailed that THCv was well tolerated, and its effects were subjectively similar to those of a placebo. Unlike THC, THCv did not significantly increase psychotic symptoms, paranoia, or impair short-term memory.

Specifically, THC impaired delayed verbal recall, a deficit not observed with THCv, suggesting that THCv may have a protective effect against some of THC’s cognitive impairments. 

Additionally, THCv countered the THC-induced increase in heart rate. Most participants (nine out of 10) reported that the effects of THC were subjectively weaker or less intense when combined with THCv (all compared to the placebo condition). However, the combination of THCv and THC was associated with a significant increase in memory intrusions, highlighting a complex interaction between THCv and THC on cognitive functions.

THCTHCv
Psychoactive EffectHigh (Euphoria)Low to Moderate
Potential Therapeutic ApplicationsPain, Muscle Spasticity, Glaucoma, Insomnia, Low Appetite, Nausea, AnxietyBlood Sugar, Insulin Resistance, Weight Loss, Panic Attacks
Appetite EffectIncreasesSuppresses
Anxiety EffectCan induce at high dosesMay reduce
Legal StatusSchedule I substance under the Controlled Substances Act; legal status varies at state level (with at least 38 states with medical access and 24 with recreational)Complex; Any hemp-derived product containing less than 0.3% THC is technically permissible, but this is still up for debate.

Effects of THCv

The effects of THCv are usually described in comparison to the more psychoactive ones from THC. This lesser-known cannabinoid is far less psychoactive than its better-known cousin. As mentioned, when used together, THCv may profoundly reduce the intense effects of THC.

Phylos Biosciences recently published a study whereby research participants were given unmedicated placebo gummies, THC-only gummies, and gummies infused with an extract from their proprietary Get Sh!t Done™ (GSD) strain (a 2:1 THCv-THC strain developed by Phylos). 

As one of the first studies conducted on the compound with human participants, its results are some of the first to describe the specific effects created by using THCv and THC together. According to their findings, 20 percent more participants felt energized after consuming the THCv-THC gummy compared with the placebo, and 40 percent reported enjoying their daily activities more with this combination than with the placebo. 

Interestingly, although THCv is often called the “diet weed” because of its supposed appetite suppressant effects, this study found that “Both GSD and THC-only gummies increased activity, exercise performance, motivation, and well-being compared to placebo.” This result perhaps indicates that THCv may not be able to drown out the strong appetite-stimulating effects of THC. Results from a pure THCv experience may be different.

Ralph Risch, CEO at Phylos Bioscience, opened up about what they’ve heard quantitatively about their unique THCv-THC GSD strain: “We hear consistently that people love how functional it is. And, you know, in a sense, it’s like the true sativa that everybody’s been looking for, but without the anxiety, without the munchies.” He said, “It has all those great uplifting vibes, but I didn’t want to raid my fridge.”

Technically, yes, but in practice, this is a highly divisive legal subject. At the federal level, according to Stark & Stark Attorneys at Law, “Simply put, any extracts or derivatives derived from hemp that contain no more than 0.3% delta-9 THC are federally permissible.” 

However, this is widely used as a loophole to skirt cannabis’ strict Schedule 1 status. Alongside other hemp-derived compounds like delta-8 and delta-9, the popularity of hemp-derived THCv-rich consumer products is on the rise. As more novel cannabinoids enter the market, an increasing number of state legislatures have passed regulations (or outright bans) on synthetic or psychoactive cannabinoids. 

For example, in 2022, Arizona passed Bill 1715, which banned the manufacture and sale of any hemp-derived compounds. If there are laws around delta-8, HHC, and the like, THCv often gets rolled into the legislation as well. With the federal rescheduling of cannabis looming and the Food and Drug Administration mulling new rules for hemp products, the future of all cannabinoids is in flux.

Where Does THCv Come From?

THCv is a minor cannabinoid and a propyl analog of Δ9-THC. Its journey begins as cannabigerovarin acid (CBGVA), then gradually synthesizes into tetrahydrocannabivarin (THCVA) throughout the plant’s maturation. Other cannabinoids follow this same path of transformation. For example, cannabigerol acid (CBGA) transforms into CBDA and THCA.

THCVA drops the molecular acid component during its final conversion following decarboxylation. Decarboxylation, commonly called decarbing, is the process of applying heat over time to transform one cannabinoid into another. Decarbing can either happen during the extraction process or through incineration or vaporization (smoking, vaping). Once THCVA is exposed to heat, the molecule transforms into THCv.

THCv Strains 

Unlike a few of the more recent novel cannabinoids now popping up at gas stations and online, THCv is a naturally occurring one. Of course, in most strains, THCv only appears in minimal and commercially nonviable amounts to make them a good prospect for THCv-rich extraction.

Are there strains with truly noticeable levels of THCv? Supposedly, Doug’s Varin is a strain of cannabis known to produce higher levels of THCv. There is a lot of online chatter about its “high levels of THCv,” but most of these claims are unsubstantiated. Another strain, Pink Boost Goddess, also usually develops a noticeable THCv profile, yet this tends to hover around the five percent mark.

Yet, there has been a new development in the naturally produced THCv arena. As the first in its rare cannabinoid line, Phylos Biosciences has successfully developed a genuinely THCv-rich strain, which they’ve named “Get Sh!t Done™ (GSD). (The genetics are now available under their company Natural Natural).

Alisha Holloway, PhD, Chief Scientific Officer at Phylos, explained that when they started this project, “We found some plants with THCv at 4 percent, and so it does occur naturally. But, it’s rare.” The Phylos team then turned to identifying which cannabis genes were responsible for the development of this cannabinoid.

According to Holloway, they discovered “the place in the genome that can be used as kind of a flag post for whether the plant produces THCv or not.” As the team discovered, several genes are responsible for this cannabinoid pattern. With the genetic markers in hand, Holloway introduced it to their breeding program, where they could “select for plants that would have high THCv and higher ratios of THCv compared to THC.”

The result is GSD, which has a two-to-one ratio of THCv to THC. Now, working with producers in Canada and the US, they are seeing GSD plants contain an unprecedented 20 percent THCv and 10 percent THC. 

How is THCv made?

Like most cannabinoids, THCv can also be replicated or synthesized in a lab. There are only a handful of pharmaceutical producers of THCv worldwide, and its distribution is highly regulated based on its relationship with THC. Isolations are available as Certified Research Materials (CRMs), but pure THCv isolates were not in production for commercial applications at the time of writing.

MilliporeSigma Canada Co. and Cerilliant both distribute THCv for research purposes. Its average price point as a CRM would make it financially prohibitive for commercial applications.

But, as mentioned, we live in a world where hemp-derived cannabinoids are getting synthesized into secondary or tertiary cannabinoids in a lab. Cannabidiol (CBD) is now delta-8 THC, THC-O, and even delta-9 THC. It shouldn’t come as a surprise that this is the same game getting played for THCv.

According to Holloway, manufacturers can use CBDV to create THCv by merging cannabinoids via a chemical reaction. But, she says, “Reactions can produce molecules that look like naturally occurring phytocannabinoids but are actually isomers. Isomers have the same chemical formula but a different arrangement. These isomers can be harmful and have not been fully studied. In addition to isomers, other harmful molecules can be created in the process.” 

So, despite the fact that hemp-derived THCv gummies, tinctures, and other isolate-infused products are popping up across the country, the challenge is that the process of creating them isn’t well understood. Remember, even if they are tested, the tests only look for expected and known molecules like CBD and THC. What happens when these chemical reactions create isomers entirely outside the scope of the standard COA?

THCv Research: A Roundup of Current Areas of Interest

The rapid spread of legalized cannabis has meant an equally rapid evolution of the research. Scientific studies no longer focus strictly on delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). It is moving into the hundreds of other lesser-known cannabis-derived compounds, including THCv.

Beyond its exciting interaction with the endocannabinoid receptors, THCv also interacts with a non-cannabinoid receptor, 5HT1A. This relationship could also be attributed to its antipsychotic effects.

Although in the very early stages of study, THCv holds the potential for several other therapeutic applications:

Known Anticonvulsant

Along with Δ9-tetrahydrocannabinolic acid (THCA), CBD, and cannabidivarin (CBDV), THCv is another known anticonvulsant agent. Thus far, only one study has identified this therapeutic characteristic in lab animals.

Neuroprotective Qualities

In an animal model of Parkinson’s Disease, THCv has “a promising pharmacological profile.” Acute administration of this cannabinoid improved the symptoms of the disease, including reducing motor inhibitions. The authors attributed these benefits to THCv’s antioxidant properties as well as the way this cannabinoid blocks CB1 receptors while activating CB2 receptors.

Improves Insulin Sensitivity

In a dietary-induced mouse model of diabetes, THCv improved insulin sensitivity, as published in a preliminary study in 2013 in the Journal of Nutrition & Diabetes. According to the authors, “THCV did not significantly affect food intake or body weight gain in any of the studies but produced an early and transient increase in energy expenditure.”

Known as the Diet cannabinoid, THCv effects on appetite are still in the preliminary phase of study.

THCv has been getting a ton of attention as a diet cannabinoid. But is it really the skinny cannabinoid all the clickbaity news seems to suggest it is? There has been so much attention on the “Ozempic of Weed,” as one article put it, that the topic of THCv and weight loss deserves a larger section.

As of the time of writing, there have really only been three studies exploring THCv for weight loss and obesity, including the study mentioned above on insulin sensitivity. 

Originally, in 2009, a study was published in the British Journal of Pharmacology, which showed a reduction of food intake among free-feeding lab mice given THCv. The authors concluded that “the phytocannabinoid Δ9-THCV is a novel compound with hypophagic properties and a potential treatment for obesity.”

The only study working with humans was published in 2015 in the International Journal of Int J Neuropsychopharmacology. Researchers used a within-subject, double-blind design and worked with 20 healthy volunteers who received a single dose of 10 mg THCv and a placebo across two sessions. 

Despite no significant differences in subjective ratings of pleasantness, intensity, or desire for the stimuli between treatments, THCv notably increased neural responses to chocolate in regions associated with reward. It also increases aversive stimuli in response to moldy strawberries.

These results demonstrate that THCv amplifies neural responses to both rewarding and aversive stimuli, and the authors note it could offer novel potential therapeutic value for obesity management with a possibly reduced risk of depressive side effects.

The Rise of THCv: No Longer Just a Minor Cannabinoid

Thanks to the work by Phylos, THCv is no longer regulated as a strictly minor cannabinoid or a synthesized hemp-derived cannabinoid. With their GSD strain now hitting 20 percent THCv, this cannabinoid could be getting much more attention for therapeutic applications or even just as a less-sleepy, less-intense THC alternate among recreational cannabis consumers.