Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol

Bhattacharyya, Sagnik; Fusar‐Poli, Paolo; Borgwardt, Stefan; Martín‐Santos, Rocío; Nosarti, Chiara; O'Carroll, C.; Allen, Paul; Seal, Marc L.; Fletcher, Paul C.; Crippa, José Alexandre de Souza; Giampietro, Vincent; Mechelli, Andrea; Atakan, Zerrin; McGuire, Philip

doi:10.1001/archgenpsychiatry.2009.17

Cited by 225 publications

(140 citation statements)

References 47 publications

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“…Oral CBD (300-600 mg) alone has been reported to produce mild sedative and anxiolytic effects in some studies (Zuardi et al, 1993;Crippa et al, 2004Crippa et al, , 2011Bergamaschi et al, 2011a, b), whereas most report no measurable psychoactivity (Benowitz et al, 1980;Borgwardt et al, 2008;Bhattacharyya et al, 2009;Winton-Brown et al, 2011;see Niesink and van Laar, 2013). When combined with THC, some have shown that (1) smoked CBD (150 μg/kg) attenuated the 'euphoric' effects of smoked THC (25 μg/kg; Dalton et al, 1976) and (2) oral CBD (1 mg/kg) reduced spontaneous reports of oral THC intoxication (Zuardi et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

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

Haney

Malcolm

Babalonis

et al. 2015

Neuropsychopharmacol

179

183

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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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Section: Introductionmentioning

confidence: 99%

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

Haney

Malcolm

Babalonis

et al. 2015

Neuropsychopharmacol

179

183

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“…While the precise neuroanatomical regions responsible for CBD's actions are not known, considerable evidence implicates the nucleus accumbens (NAc) as an important site for CBD's modulatory effects on various cognitive and behavioral phenomena (Guimarães et al, 2004;Bhattacharyya et al, 2009;Valvassori et al, 2011;Mijangos-Moreno et al, 2014;Pedrazzi et al, 2015). For example, CBD attenuates THCinduced dysregulation of the ventral striatum during verbal recall tasks (Bhattacharyya et al, 2009) and increases c-fos and adenosine levels in rodent NAc (Guimarães et al, 2004;Mijangos-Moreno et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…For example, CBD attenuates THCinduced dysregulation of the ventral striatum during verbal recall tasks (Bhattacharyya et al, 2009) and increases c-fos and adenosine levels in rodent NAc (Guimarães et al, 2004;Mijangos-Moreno et al, 2014). In addition, CBD blocks amphetamine-induced oxidative stress in the NAc (Valvassori et al, 2011) and intra-NAc CBD attenuates amphetamineinduced deficits in prepulse inhibition (Pedrazzi et al, 2015;Renard et al, 2016b).…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

Norris

Loureiro

Kramar

et al. 2016

Neuropsychopharmacol

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Emerging evidence suggests that the largest phytochemical component of cannabis, cannabidiol (CBD), may possess pharmacotherapeutic properties in the treatment of neuropsychiatric disorders. CBD has been reported to functionally interact with both the mesolimbic dopamine (DA) and serotonergic (5-HT) receptor systems. However, the underlying mechanisms by which CBD may modulate emotional processing are not currently understood. Using a combination of in vivo electrophysiological recording and fear conditioning in rats, the present study aimed to characterize the behavioral, neuroanatomical, and pharmacological effects of CBD within the mesolimbic pathway, and its possible functional interactions with 5-HT and DAergic transmission. Using targeted microinfusions of CBD into the shell region of the mesolimbic nucleus accumbens (NASh), we report that intra-NASh CBD potently blocks the formation of conditioned freezing behaviors. These effects were challenged with DAergic, cannabinoid CB1 receptor, and serotonergic (5-HT 1A ) transmission blockade, but only 5-HT 1A blockade restored associative conditioned freezing behaviors. In vivo intra-ventral tegmental area (VTA) electrophysiological recordings revealed that behaviorally effective doses of intra-NASh CBD elicited a predominant decrease in spontaneous DAergic neuronal frequency and bursting activity. These neuronal effects were reversed by simultaneous blockade of 5-HT 1A receptor transmission. Finally, using a functional contralateral disconnection procedure, we demonstrated that the ability of intra-NASh CBD to block the formation of conditioned freezing behaviors was dependent on intra-VTA GABAergic transmission substrates. Our findings demonstrate a novel NAc → VTA circuit responsible for the behavioral and neuronal effects of CBD within the mesolimbic system via functional interactions with serotonergic 5-HT 1A receptor signaling.

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“…Under experimental conditions, a single dose of its main psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), can result in the acute induction of transient psychotic symptoms in man similar to that seen under the influence of cannabis, and these acute effects have been linked to its effects on prefrontal, medial temporal and striatal function (Bhattacharyya et al, 2009;D'Souza et al, 2008D'Souza et al, , 2004.…”

Section: Introductionmentioning

confidence: 99%

Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date

Sami

Rabiner

Bhattacharyya

2015

European Neuropsychopharmacology

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Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol

Abstract: The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms, respectively.

Cited by 225 publications

References 47 publications

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

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

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date

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