Summary
Tetrahydrocannabivarin (THCV), first discovered in 1971, is similar structurally to THC because it has a tail that is just two carbons shorter but its effects are quite different. Instead of binding to the CB1 receptor, THCV seems to blocks access to the CB1 receptor while also binding strongly to the CB2 receptor although its exact effects at the CB1 receptor are still not completely understood. Early studies demonstrated its anticonvulsant effects, probably via the CB1 receptor. Another focus has been its potential help for diabetes, nausea, and obesity. In a mouse model of obesity, THCV lowered food intake and weight gain as well as helping to lessen insulin sensitivity. In humans, 10 mg of THCV caused the brain to respond less strongly to tempting foods like chocolate. It’s been looked at in humans for treating diabetes and has a pharmaceutical patent for that application. In the brain, it helps to calm neural transmission, lessens obsessive compulsive behaviors and schizophrenic behaviors in animal models, causes neuroprotection in a model of Parkinson’s and helps lessen negative side effects from the Parkinson’s treatment drug L-DOPA via antioxidant effects. THCV has also been researched for inflammatory and neuropathic pain, reduced contractions in the bladder, reduced fat levels in nonalcoholic fatty liver disease, antimalarial activity, reduced sebum production to help with acne, and protection from some of the negative side effects of THC.
Timeline of Research
2022: A review of the dosing of THC, CBD & THCV for various conditions
A Systematic Review of Medical Cannabinoids Dosing in Human
https://pubmed.ncbi.nlm.nih.gov/36411116
2022: In lung cells, a mix of CBD, CBG & THCV worked synergistically with non-steroidal anti-inflammatory drugs like ibuprofen to reduce inflammation
Phytocannabinoids Act Synergistically with Non-Steroidal Anti-Inflammatory Drugs Reducing Inflammation in 2D and 3D In Vitro Models
https://pubmed.ncbi.nlm.nih.gov/36559009/
2022: In a rat model of neuropathic pain, CBD & THCV worked together to reduce pain & protect the neurons via the CB1 receptor & a serotonin receptor
Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents
https://pubmed.ncbi.nlm.nih.gov/35303507/
2022: In a mouse model of malaria, cannabis leaf extracts lowered parasite infestation & THCV had the highest binding energy to the protein microtubules of the parasite
Evaluation of anti-malarial activity and GC–MS finger printing of cannabis: An in-vivo and in silico approach
https://www.sciencedirect.com/science/article/pii/S2468227622000175
2020: In mice with Parkinson's, THCV helped with the dyskinesia resulting from L-DOPA treatment
Beneficial effects of the phytocannabinoid Δ9-THCV in L-DOPA-induced dyskinesia in Parkinson's disease
https://www.sciencedirect.com/science/article/pii/S0969996120301674
2020: Two Chinese hemp cultivars, high in varins like CBDV, CBDVA, THCVA & THCV, had strong antimicrobial & antioxidant activity
Antioxidant and antimicrobial activity of two standardized extracts from a new Chinese accession of non‐psychotropic Cannabis sativa L.
https://onlinelibrary.wiley.com/doi/10.1002/ptr.6891
2020: A commentary on THCV for diabetes
Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes
https://pubmed.ncbi.nlm.nih.gov/33526143
2016: In healthy humans, 10 mg of THCV for 5 days was not differentiable from the placebo & when THC was administered on the last day, THCV protected from delayed memory recall, inhibited the increased heart rate & caused a weaker THC experience but increased memory errors
The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial
https://pubmed.ncbi.nlm.nih.gov/26577065
2016: In human sebocytes model of acne, CBC & THCV suppressed lipid synthesis, CBDV had only minor effects & CBG & CBGV increased it - CBC, CBDV & THCV reduced arachidonic acid-induced 'acne-like' lipogenesis – THCV suppressed proliferation – all cannabinoids exerted remarkable anti-inflammatory effects
Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment
https://www.ncbi.nlm.nih.gov/pubmed/27094344
2016: In humans with type 2 diabetes, 13 weeks of 100 mg of CBD led to less resistin hormone & more glucose-dependent insulinotropic peptides – also tested THCV and found it promising – but neither treatments had a significant impact on endpoints – 62 participants in a double‐blind RCT
Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study
https://www.ncbi.nlm.nih.gov/pubmed/27573936
2015: In brain tissue & a rat model of schizophrenia, THCV reduced stereotyped behaviour; decreased immobility time in the forced swim test & normalized hyperlocomotor activity, social behaviour & cognitive performance at least partially via the serotonin 5-HT₁A receptors
The phytocannabinoid, Δ⁹-tetrahydrocannabivarin, can act through 5-HT₁A receptors to produce antipsychotic effects
https://pubmed.ncbi.nlm.nih.gov/25363799
2015: In a zebrafish & mouse model of non-alcoholic fatty liver disease, CBD & THCV reduced lipid levels & hepatosteatosis (the accumulation of fat in the liver)
Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis
https://www.ncbi.nlm.nih.gov/pubmed/25595882/
2014: In a healthy human study of neural rewards to food, 10 mg of THCV did not change their subjective rating of food but it did increases the response to chocolate in several brain regions as well as the response to aversive food in other brain areas
Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin on food reward and aversion in healthy volunteers
https://pubmed.ncbi.nlm.nih.gov/25542687
2013: In rats with nausea, CBDV & THCV helped but not via reverse CB1 agonism
Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ(9) -tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats
https://pubmed.ncbi.nlm.nih.gov/23902479
2013: In obese mice, THCV ameliorated insulin sensitivity
The cannabinoid Δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity
https://pubmed.ncbi.nlm.nih.gov/23712280/
2012: In a rodent model of obsessive-compulsive disorder, CBD helped with obsessive behaviors & CBD, CBDV, THCV & CBG all penetrated into the brain whether via oral or abdominal injection
Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ⁹-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour
https://www.ncbi.nlm.nih.gov/pubmed/21796370
2011: In a rat model of Parkinson’s, THCV caused neuroprotection & symptom relief via glutamate, CB2 & antioxidation
Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ9-THCV in animal models of Parkinson's disease
https://www.ncbi.nlm.nih.gov/pubmed/21323909
2011: CBDA inhibits NAAA – potent at inhibiting AEA reuptake – inhibits DAGLα – agonist at TRPA1 channels – binds to TRPM8
Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes
https://www.ncbi.nlm.nih.gov/pubmed/21175579
2010: In a mouse model of pain & inflammation, THCV decreased pain behaviors probably via CB1, CB2 & cyclic AMP production
The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice
https://pubmed.ncbi.nlm.nih.gov/20590571
2010: In a rat model of epileptic seizures, THCV reduced seizures, probably via the CB1 receptor
Δ⁹-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats
https://pubmed.ncbi.nlm.nih.gov/20196794
2009: In a mouse model of obesity, the CB1 antagonist AM251 suppressed food intake & weight gain as did THCV – while a THCV rich extract failed to suppress food intake & weight gain, possibly because of the THC – which was overcome by coadministration of CBD
Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice
https://pubmed.ncbi.nlm.nih.gov/19378378
2008: In cerebellum synapses, THCV lowered activity via antagonism of CB1
The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum
https://pubmed.ncbi.nlm.nih.gov/18311186
2007: In a binding assay, THCV & delta-8 THCV antagonize THC binding at CB1
The psychoactive plant cannabinoid, Delta9-tetrahydrocannabinol, is antagonized by Delta8- and Delta9-tetrahydrocannabivarin in mice in vivo
https://pubmed.ncbi.nlm.nih.gov/17245367
2006: THCV’s anticonvulsant effects
Tetrahydrocannabivarin exhibits anticonvulsant effects in a piriform cortical brain slice model of epileptiform activity
https://www.researchgate.net/publication/41571550_Tetrahydrocannabivarin_exhibits_anticonvulsant_effects_in_a_piriform_cortical_brain_slice_model_of_epileptiform_activity
2005: In a binding assay, THCV behaves as a competitive CB1 & CB2 receptor antagonist
Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist
https://pubmed.ncbi.nlm.nih.gov/16205722
1974: early human studies on CBN, CBD, CBC, THC, delta8-THC, 11-OH-THC, delta8-11-OH-THC – 7 mg of THCV felt similar to THC, estimated potency of 25%
Structure-activity relationships in man of cannabis constituents, and homologs and metabolites of delta9-tetrahydrocannabinol
https://pubmed.ncbi.nlm.nih.gov/4610598
1971: Discovery of THCV & CBDV
Cannabivarin and tetrahydrocannabivarin, two new constituents of hashish
https://pubmed.ncbi.nlm.nih.gov/4937510