Chemical Basis of Hashish Activity

Mechoulam, Raphael; Shani, A.; Edery, H.; Grunfeld, Yona

doi:10.1126/science.169.3945.611

Cited by 322 publications

(168 citation statements)

References 12 publications

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“…This regional profile of effects is largely in accordance with the distribution of CB1 cannabinoid receptors at which THC acts (Devane et al, 1988;Mechoulam et al, 1970;Glass et al, 1997;Herkenham et al, 1990Herkenham et al, , 1991a, and THC-induced alterations in activity in these areas have also been demonstrated in previous IEG and metabolic mapping studies performed in rodents (Bloom et al, 1997;ErdtmannVourliotis et al, 1999;Mailleux et al, 1994;Margulies and Hammer, 1991;McGregor et al, 1998;Whitlow et al, 2002). In addition, human imaging studies have consistently demonstrated marked alterations in activity in frontal brain regions following acute marijuana/THC intake or chronic marijuana use (Lundqvist et al, 2001;Mathew and Wilson, 1993;Mathew et al, 1997Mathew et al, , 2002O'Leary et al, 2000O'Leary et al, , 2002Volkow et al, 1996).…”

Section: Discussionsupporting

confidence: 57%

Acute Δ9-Tetrahydrocannabinol-Induced Deficits in Reversal Learning: Neural Correlates of Affective Inflexibility

Egerton

Brett

Pratt

2005

Neuropsychopharmacol

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Despite concerns surrounding the possible adverse effects of marijuana on complex cognitive function, the processes contributing to the observed cognitive deficits are unclear, as are the causal relationships between these impairments and marijuana exposure. In particular, marijuana-related deficits in cognitive flexibility may affect the social functioning of the individual and may contribute to continued marijuana use. We therefore examined the ability of rats to perform affective and attentional shifts following acute administration of D 9 -tetrahydrocannabinol (THC), the primary psychoactive marijuana constituent. Administration of 1 mg/kg THC produced marked impairments in the ability to reverse previously relevant associations between stimulus features and reward presentation, while the ability to transfer attentional set between dimensional stimulus properties was unaffected. Concurrent in situ hybridization analysis of regional c-fos and ngfi-b expression highlighted areas of the prefrontal cortex and striatum that were recruited in response to both THC administration and task performance. Furthermore, the alterations in mRNA expression in the orbitofrontal cortex and striatum were associated with the ability to perform the reversal discriminations. These findings suggest that marijuana use may produce inelasticity in updating affective associations between stimuli and reinforcement value, and that this effect may arise through dysregulation of orbitofrontal and striatal circuitry.

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Section: Discussionsupporting

confidence: 57%

Acute Δ9-Tetrahydrocannabinol-Induced Deficits in Reversal Learning: Neural Correlates of Affective Inflexibility

Egerton

Brett

Pratt

2005

Neuropsychopharmacol

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“…Preparations of Cannabis sativa have been used for medicinal and recreational purposes for at least 4000 years and extracts of C. sativa contain over 60 different pharmacologically active components the most prominent being D 9 -tetrahydrocannabinol (D 9 -THC) and cannabidiol (Mechoulam, 1970a;Mechoulam et al, 1970b;Howlett, 2002). Cannabinoids exert their effects by binding to specific receptors located in the membrane of the cell.…”

Section: Introductionmentioning

confidence: 99%

The orphan receptor GPR55 is a novel cannabinoid receptor

Ryberg

Larsson

Sjögren

et al. 2007

British J Pharmacology

1,368

1,491

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Background: The endocannabinoid system functions through two well characterized receptor systems, the CB 1 and CB 2 receptors. Work by a number of groups in recent years has provided evidence that the system is more complicated and additional receptor types should exist to explain ligand activity in a number of physiological processes. Experimental approach: Cells transfected with the human cDNA for GPR55 were tested for their ability to bind and to mediate GTPgS binding by cannabinoid ligands. Using an antibody and peptide blocking approach, the nature of the Gprotein coupling was determined and further demonstrated by measuring activity of downstream signalling pathways.Key results: We demonstrate that GPR55 binds to and is activated by the cannabinoid ligand CP55940. In addition endocannabinoids including anandamide and virodhamine activate GTPgS binding via GPR55 with nM potencies. Ligands such as cannabidiol and abnormal cannabidiol which exhibit no CB 1 or CB 2 activity and are believed to function at a novel cannabinoid receptor, also showed activity at GPR55. GPR55 couples to Ga13 and can mediate activation of rhoA, cdc42 and rac1. Conclusions: These data suggest that GPR55 is a novel cannabinoid receptor, and its ligand profile with respect to CB 1 and CB 2 described here will permit delineation of its physiological function(s).

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“…Only a few pharmacological studies on CBD were reported before the early 1970's, showing that CBD had no cannabis-like activity. 6 The number of publications increased in this decade and reached a first peak around 1975. In this period, a Brazilian research group led by Carlini, gave an important contribution, especially about the interactions of delta9-THC with other cannabinoids, including CBD.…”

Section: Introductionmentioning

confidence: 99%