In this first study of THC and THCV, THCV inhibited some of the well-known effects of THC, while potentiating others. These findings need to be interpreted with caution due to a small sample size and lack of THC-induced psychotomimetic and memory-impairing effect, probably owing to the choice of dose.

THCV was well tolerated and subjectively indistinguishable from placebo. THC did not significantly increase psychotic symptoms, paranoia or impair short-term memory, while still producing significant intoxicating effects. Delayed verbal recall was impaired by THC and only occurred under placebo condition ( Z =-2.201, p =0.028), suggesting a protective effect of THCV. THCV also inhibited THC-induced increased heart rate ( Z =-2.193, p =0.028). Nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense (χ 2 =6.4, p =0.011). THCV in combination with THC significantly increased memory intrusions ( Z =-2.155, p =0.031).

Ten male cannabis users (<25 use occasions) were recruited for this within-subjects, placebo-controlled, double-blind, cross-over pilot study. 10mg oral pure THCV or placebo were administered daily for five days, followed by 1mg intravenous THC on the fifth day.

To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers.

Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC.

References

Atakan, Z ( 2012 ) Cannabis, a complex plant: different compounds and different effects on individuals . Therapeut Adv Psychopharmacol 2: 241 – 254 .

Google Scholar SAGE Journals

Beck, AT, Epstein, N, Brown, G. ( 1988 ) An inventory for measuring clinical anxiety: psychometric properties . J Consult Clin Psychol 56: 893 – 897

Google Scholar Crossref | Medline | ISI

Bergamaschi, MM, Queiroz, RHC, Chagas, MHN. ( 2014 ) Rimonabant effects on anxiety induced by simulated public speaking in healthy humans: a preliminary report . Human Psychopharmacol 29: 94 – 99 .

Google Scholar Crossref | Medline | ISI

Boggs, DL, Kelly, DL, McMahon, RP. ( 2012 ) Rimonabant for neurocognition in schizophrenia: a 16-week double blind randomized placebo controlled trial . Schizophrenia Res 134: 207 – 210 .

Google Scholar Crossref | Medline | ISI

Carbuto, M, Sewell, RA, Williams, A. ( 2012 ) The safety of studies with intravenous Δ9-tetrahydrocannabinol in humans, with case histories . Psychopharmacology 219: 885 – 896 .

Google Scholar Crossref | Medline | ISI

Cascio, MG, Zamberletti, E, Marini, P. ( 2015 ) The phytocannabinoid, Δ 9-tetrahydrocannabivarin, can act through 5-HT 1A receptors to produce antipsychotic effects . Br J Pharmacology 172: 1305 – 1318 .

Google Scholar Crossref | Medline | ISI

Christensen, R, Kristensen, PK, Bartels, EM. ( 2007 ) Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials . Lancet. 370: 1706 – 1713 .

Google Scholar Crossref | Medline | ISI

D’Souza, DC, Perry, E, MacDougall, L. ( 2004 ) The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis . Neuropsychopharmacology 29: 1558 – 1572 .

Google Scholar Crossref | Medline | ISI

D’Souza, DC, Abi-Saab, WM, Madonick, S. ( 2005 ) Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction . Biol Psychiatry 57: 594 – 608 .

Google Scholar Crossref | Medline | ISI

D’Souza, DC, Ranganathan, M, Braley, G. ( 2008 ) Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis . Neuropsychopharmacology 33: 2505 – 2516 .

Google Scholar Crossref | Medline | ISI

Dewey, WL ( 1986 ) Cannabinoid pharmacology . Pharmacologic Revs 38: 151 – 178 .

Google Scholar Medline | ISI

Englund, A, Stone, JM, Morrison, PD ( 2012 ) Cannabis in the arm: what can we learn from intravenous cannabinoid studies? Current Pharmaceut Des 18: 4906 – 4914 .

Google Scholar Crossref | Medline | ISI

Englund, A, Morrison, PD, Nottage, J. ( 2013 ) Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment . J Psychopharmacol (Oxford) 27: 19 – 27 .

Google Scholar SAGE Journals | ISI

Freeman, D, Pugh, K, Green, C. ( 2007 ) A measure of state persecutory ideation for experimental studies . J Nervous Mental Dis 195: 781 – 784 .

Google Scholar Crossref | Medline | ISI

Gill, EW, Paton, WD, Pertwee, RG ( 1970 ) Preliminary experiments on the chemistry and pharmacology of cannabis . Nature 228: 134 – 136 .

Google Scholar Crossref | Medline | ISI

Grotenhermen, F ( 2003 ) Pharmacokinetics and pharmacodynamics of cannabinoids . Clin Pharmacokinetics 42: 327 – 360 .

Google Scholar Crossref | Medline | ISI

Hanus, LO ( 2009 ) Pharmacological and therapeutic secrets of plant and brain (endo)cannabinoids . Medicin Res Revs 29: 213 – 271 .

Google Scholar Crossref | Medline | ISI

Hillig, KW, Mahlberg, PG ( 2004 ) A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae) . Am J Botany 91: 966 – 975 .

Google Scholar Crossref | Medline | ISI

Hollister, LE ( 1974 ) Structure-activity relationships in man of cannabis constituents, and homologs and metabolites of delta9-tetrahydrocannabinol . Pharmacology 11: 3 – 11 .

Google Scholar Crossref | Medline | ISI

Horder, J, Cowen, PJ, Di Simplicio, M. ( 2009 ) Acute administration of the cannabinoid CB1 antagonist rimonabant impairs positive affective memory in healthy volunteers . Psychopharmacology 205: 85 – 91 .

Google Scholar Crossref | Medline | ISI

Horder, J, Browning, M, Di Simplicio, M. ( 2012 ) Effects of 7 days of treatment with the cannabinoid type 1 receptor antagonist, rimonabant, on emotional processing . J Psychopharmacol (Oxford) 26:, 125 – 132 .

Google Scholar Crossref | Medline | ISI

Lichtman, AH ( 2000 ) SR 141716A enhances spatial memory as assessed in a radial-arm maze task in rats . Euro J Pharmacol 404: 175 – 179 .

Google Scholar Crossref | Medline | ISI

Matthews, G, Jones, DM, Chamberlain, AG ( 1990 ) Refining the measurement of mood: The UWIST Mood Adjective Checklist . Br J Psychol 81: 17 – 42 .

Google Scholar Crossref | ISI

McPartland, JM, Duncan, M, Di Marzo, V. ( 2015 ) Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review . Br J Pharmacol 172: 737 – 753 .

Google Scholar Crossref | Medline | ISI

Mehmedic, Z, Chandra, S, Slade, D. ( 2010 ) Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008 . J Forensic Sci 55: 1209 – 1217 .

Google Scholar Crossref | Medline | ISI

Morgan, CJA, Schafer, G, Freeman, TP. ( 2010 ) Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study [corrected] . Br J Psychiatry:J Mental Sci 197: 285 – 290 .

Google Scholar Crossref | Medline | ISI

Morrison, PD, Stone, JM ( 2011 ) Synthetic delta-9-tetrahydrocannabinol elicits schizophrenia-like negative symptoms which are distinct from sedation . Human Psychopharmacol 26: 77 – 80 .

Google Scholar Crossref | Medline | ISI

Morrison, PD, Zois, V, McKeown, DA. ( 2009 ) The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning . Psychol Med 39: 1607 – 1616 .

Google Scholar Crossref | Medline | ISI

Morrison, PD, Nottage, J, Stone, JM. ( 2011 ) Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms . Neuropsychopharmacology 36: 827 – 836 .

Google Scholar Crossref | Medline | ISI

Naef, M, Russmann, S, Petersen-Felix, S. ( 2004 ) Development and pharmacokinetic characterization of pulmonal and intravenous delta-9-tetrahydrocannabinol (THC) in humans . J Pharmaceut Sci 93: 1176 – 1184 .

Google Scholar Crossref | Medline | ISI

Nissen, SE, Nicholls, SJ, Wolski, K. ( 2008 ) Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial . JAMA 299: 1547 – 1560 .

Google Scholar Crossref | Medline | ISI

Pertwee, RG ( 2008 ) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin . Br J Pharmacol 153: 199 – 215 .

Google Scholar Crossref | Medline | ISI

Pertwee, RG, Thomas, A, Stevenson, LA. ( 2007 ) The psychoactive plant cannabinoid, Delta9-tetrahydrocannabinol, is antagonized by Delta8- and Delta9-tetrahydrocannabivarin in mice in vivo . Br J Pharmacol 150: 586 – 594 .

Google Scholar Crossref | Medline | ISI

Potter, DJ ( 2014 ) A review of the cultivation and processing of cannabis (Cannabis sativa L.) for production of prescription medicines in the UK . Drug Test Anal 6: 31 – 38 .

Google Scholar Crossref | Medline | ISI

Rock, EM, Sticht, MA, Duncan, M. ( 2013 ) 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 . B J Pharmacol 170: 671 – 678 .

Google Scholar Crossref | Medline | ISI

Schubart, CD, Sommer, IEC, van Gastel, WA. ( 2011 ) Cannabis with high cannabidiol content is associated with fewer psychotic experiences . Schizophrenia Res 130: 216 – 221 .

Google Scholar Crossref | Medline | ISI

Shiflett, MW, Rankin, AZ, Tomaszycki, ML. ( 2004 ) Cannabinoid inhibition improves memory in food-storing birds, but with a cost . Proc R Soc Biol Sci 271: 2043 – 2048 .

Google Scholar Crossref | Medline | ISI

Stefanis, NC, Hanssen, M, Smirnis, NK. ( 2002 ) Evidence that three dimensions of psychosis have a distribution in the general population . Psychol Med 32: 347 – 358 .

Google Scholar Crossref | Medline | ISI

Stone, JM, Morrison, PD, Brugger, S. ( 2012 ) Communication breakdown: delta-9 tetrahydrocannabinol effects on pre-speech neural coherence . Mol Psychiatry 17: 568 – 569 .

Google Scholar Crossref | Medline | ISI

Terranova, JP, Storme, JJ, Lafon, N. ( 1996 ) Improvement of memory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141716 . Psychopharmacology 126: 165 – 172 .

Google Scholar Crossref | Medline | ISI

Thomas, A, Stevenson, LA, Wease, KN. ( 2005 ) Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist . Br J Pharmacol 146: 917 – 926 .

Google Scholar Crossref | Medline | ISI

Tudge, L, Williams, C, Cowen, PJ. ( 2014 ) Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin (THCv) on food reward and aversion in healthy volunteers . Int J Neuropsychopharmacol 18: ii .

Google Scholar ISI

Wargent, ET, Zaibi, MS, Silvestri, C. ( 2013 ) The cannabinoid Δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity . Nutr Diabetes 3: e68 .

Google Scholar Crossref | Medline | ISI