Cannabidiol interferes with the effects of Δ9-tetrahydrocannabinol in man

Karniol, Isac Germano; Shirakawa, Itiro; Kasinski, Nelson; Pfeferman, Abraham; Carlini, E. A.

doi:10.1016/0014-2999(74)90129-0

Cited by 295 publications

(193 citation statements)

References 16 publications

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“…This effect has been attributed to THC. In agreement with the initial reports showing antagonism of THC-induced psychotomimetic effects [31,87,88], the presence of CBD in Cannabis strains has been shown to be protective against the occurrence of psychotic-like reactions and cognitive impairment [108][109][110]. In this context, Di Forti et al [111] found that the use of Cannabis containing high THC-and low CBD concentration was associated with a higher risk of a first psychotic episode.…”

Section: Cannabidiol and Psychosissupporting

confidence: 66%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

342

227

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Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D 9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca 2þ ) increase, etc.), on CBD behavioural effects.

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Section: Cannabidiol and Psychosissupporting

confidence: 66%

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Campos

Moreira

Gomes

et al. 2012

Phil. Trans. R. Soc. B

342

227

View full text Add to dashboard Cite

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“…Although CBD does not reduce THC's positive subjective effects (ie, ratings of 'high' or 'stoned'), there is evidence that it may reduce anxiety or transient psychosis-like side-effects of THC observed in infrequent cannabis smokers or when administered alone to patients with anxiety or psychosis (Bhattacharyya et al, 2010;Crippa et al, 2011;Bergamaschi et al, 2011a, b;Leweke et al, 2012;see Niesink and van Laar, 2013). Older studies report that CBD changes the type of psychological reaction induced by THC in infrequent cannabis smokers, reducing their anxiety and thereby rendering THC more enjoyable (eg, Karniol et al, 1974). Daily cannabis smokers rarely have anxiety and psychosis-like symptoms following active cannabis administration, and although there were three instances of anxiety in the present study following cannabis administration, there were too few to assess whether CBD altered these experiences.…”

Section: Discussionmentioning

confidence: 57%

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

Haney

Malcolm

Babalonis

et al. 2015

Neuropsychopharmacol

172

180

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Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ 9 -tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30-5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n = 31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n = 8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of 'High', 'Good Effect', ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis.

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“…The anxiolytic effects of CBD in humans were first demonstrated in the context of reversing the anxiogenic effects of THC. CBD reduced THC-induced anxiety when administered simultaneously with this agent, but had no effect on baseline anxiety when administered alone [99,100]. Further studies using higher doses supported a lack of anxiolytic effects at baseline [101,107].…”

Section: Human Experimental and Clinical Studies Evidence From Acute mentioning

confidence: 82%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

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Cannabidiol interferes with the effects of Δ9-tetrahydrocannabinol in man

Cited by 295 publications

References 16 publications

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

Cannabidiol as a Potential Treatment for Anxiety Disorders

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