THCV is a phytocannabinoid analogous to THC. THCV have different interactions with CB1 and CB2 compared to THC, and yields some opposite effects like the suppression of appetite. In addition, THCV is reported to have anti-epileptic and anti-psychotic effects and shows potential to help in a wide list of diseases, like type 2 Diabetes or Obesity.
THCV is synthesized through decarboxylation of tetrahydrocannabivarinic acid (THCVA). THCVA is synthesized from cannabigerovarin (CBGV) by acid synthase. CBGV is synthesized through decarboxylation of cannabigerovaric acid (CBGVA). CBGVA is synthesized from divarinolic acid and geranyl-pyrophosphate.
THCV is degraded through oxydation to cannabivarin (CBV).
THCV binds to CB1 and CB2 receptors. It acts as a partial agonist of CB2 receptor. However, it is not clear how specifically interacts with CB1. In vitro studies show antagonist effects while in vivo studies suggest neutral receptor antagonist effects (McPartland, Duncan, Di Marzo, & Pertwee, 2015; Morales, Hurst, & Reggio, 2017; Thomas et al., 2005).
THCV acts as antagonist of TRPM8 and also activates TRPV1, TRPV2, TRPV3 and TRPV4, suggesting several potential therapeutic effects, including acne treatment and gastrointestinal inflammation (L. De Petrocellis et al., 2012; Luciano De Petrocellis et al., 2011; Oláh et al., 2016)
THCV showed potential to treat bladder dysfunctions (Pagano et al., 2015)
In one study THCV reduced inflammatory leukocyte recruitment (Makwana et al., 2015)
Functional Gastro-Intestinal Disorders
Apart from THC, (relatively) non-psychotropic cannabinoids such as THCV, CBD and CBG were found to have anti-inflammatory effects in experimental intestinal inflammation (Alhouayek and Muccioli, 2012).
Synthetic THCV showed protective effects against liver damage (Bátkai et al., 2012)
A comparative study into the topical anti-inflammatory activity of cannabinoids (on croton oil-inflamed skin in mice) showed that Δ8THC, Δ9THC and THCV are about half as effective in reducing inflammation as Indometacin (a commonly used Non-steroid anti-inflammatory drug), but approximately 5 times more effective than CBCV and CBD. CBC and CBDV had no appreciable anti-inflammatory activity (Tubaro et al., 2010).
THCV significantly reduced epilepsy seizure incidence starting with doses of 0.25 mg/kg in animal models. THCV shows antiepileptiform and anticonvulsant properties, probably related to its activity in CB1 receptors (Gaston & Friedman, 2017; Hill et al., 2010).
In healthy human volunteers, 10 mg oral THCV reduced functional network connectivity in the brain (measured by fMRI)(Rzepa et al., 2015).
THCV inhibits nitrite production, showing anti-inflamatory and immunomodulatory effects (Bolognini et al., 2010; Romano et al., 2016)
THCV induced hypophagia and reduction in body weight at low doses (from 3mg/kg), suggesting a possible treatment for Obesity and metabolic syndrome. THC combination with THCV would delete these effects, but they are rescued by combining them with CBD (Riedel et al., 2009; Silvestri et al., 2015; Wargent et al., 2013).
In contrast to Rimonabant, THCV does not cause nausea but maintains the anti-Obesity potential (Rock, Sticht, Duncan, Stott, & Parker, 2013). Oral dose administration of 10mg of THCV reduces resting state functional connectivity in brain areas that are usually overactivated in obese individuals. Also, it activates areas which have reduced activity linked to Obesity (Rzepa, Tudge, & McCabe, 2015). The same dose was used in another study showing increased brain activity in Obesity related areas when presenting different types of food stimuli, suggesting also a possible therapeutic potential to treat Obesity (Tudge, Williams, Cowen, & McCabe, 2015).
Antioxidant effects of THCV have been related to an attenuation of motor inhibition through CB2 receptors in animal models of Parkinson´s Disease (PD), suggesting an interesting approach to ameliorate PD symptoms and even to delay disease progression (García et al., 2011).
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