Health aspects of cannabis

Le, Hollister

doi:10.1016/0378-8741(87)90030-4

Cited by 204 publications

(307 citation statements)

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“…Cannabinoids are the primary psychoactive constituents of marijuana that have profound effects on pain perception, neural convulsions, memory and motor coordination [1,2]. Their effects are most commonly mediated by the CB1 cannabinoid receptor (CB1R), which is highly expressed in a variety of brain regions, including the hypothalamus [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

et al. 2009

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a b s t r a c tUsing immortalized hypothalamic GT1-7 neurons, which express the CB1 cannabinoid receptor (CB1R) and three Ca 2+ channel types (T, R and L), we found that the CB1R agonist WIN 55,212-2 inhibited the voltage-gated Ca 2+ currents by about 35%. The inhibition by WIN 55,212-2 (10 M) was reversible and prevented by nifedipine (3 M), suggesting a selective action on L-type Ca 2+ channels (LTCCs). WIN 55,212-2 action exhibited all the features of voltage-independent Ca 2+ channel modulation: (1) no changes of the activation kinetics, (2) equal depressive action at all potentials and (3) no facilitation following strong prepulses. At variance with WIN 55,212-2, the CB1R inverse agonist AM-251 (10 M) caused 20% increase of Ca 2+ currents. The inhibition of LTCCs by WIN 55,212-2 was prevented by overnight PTX-incubation and by intracellular perfusion with GDP-␤-S. The latter caused also a 20% Ca 2+ current up-regulation. WIN 55,212-2 action was also prevented by application of the PKA-blocker H89 or by loading the neurons with 8-CPT-cAMP. Our results suggest that LTCCs in GT1-7 neurons are partially inhibited at rest due to a constitutive CB1R activity removed by AM-251 and GDP-␤-S. Activation of CB1R via PTX-sensitive G proteins and cAMP/PKA pathway selectively depresses LTCCs that critically control the synchronized spontaneous firing and pulsatile release of gonadotropin-releasing hormone in GT1-7 neurons.

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Section: Introductionmentioning

confidence: 99%

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

et al. 2009

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“…Cannabis sativa preparations, the main psychoactive ingredient of which is Δ9-THC, produce intoxication characterized by sedation, cognitive dysfunction, failure to consolidate short-term memory, alteration in time assessment, perceptual changes, motor incoordination and poor executive function (Abood and Martin 1992;Dewey 1986;Hollister 1986;Pertwee 1988). In addition to exogenous cannabinoids, endocannabinoids including andamide and noladin ether, have also been identified.…”

Section: Introductionmentioning

confidence: 99%

Association study of the CNR1 gene exon 3 alternative promoter region polymorphisms and substance dependence

Herman

Kranzler

Cubells

et al. 2006

American J of Med Genetics Pt B

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An alternative promoter producing a novel 5′-untranslated region of cannabinoid receptor mRNA has recently been described in CNR1, the gene encoding the cannabinoid receptor protein. Single nucleotide polymorphisms (SNPs) adjacent to this site were reported to be associated with polysubstance abuse (Zhang et al. 2004). We examined the association of 4 SNPs (rs6928499, rs806379, rs1535255, rs2023239) in the distal region of intron 2 of CNR1 both with individual substance dependence diagnoses (i.e., alcohol, cocaine, and opioids), as well as with polysubstance dependence. The study samples consisted of European American and African American subjects with drug and or alcohol dependence (n=895), and controls (n = 472). Subjects were grouped as polysubstance dependent, opioid dependent, cocaine dependent, cannabis dependent and alcohol dependent. There was a modest association of marker rs1535255 with alcohol dependence, respectively (P=0.04), though with correction for multiple phenotype comparisons, this effect was not considered statistically significant. These findings fail to replicate the original report of an association between SNPs adjacent to an alternative CNR1 exon 3 transcription start site and polysubstance abuse.

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“…D-9-tetrahydrocannibinol (THC) has consistently been found to affect verbal learning and memory (see, Hollister, 1986;Miller and Branconnier, 1983;Ameri, 1999, for a review), and such impairments are likely to underpin difficulties with more complex mental activities such as arithmetic and planning (Casswell and Marks, 1973;Chait and Perry, 1994). However, the evidence that THC particularly impairs working memory in human subjects is slightly more equivocal, with positive (Heishman et al, 1997;D'Souza et al, 2004) but also recent negative findings (Curran et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Low Doses of Δ-9 Tetrahydrocannabinol (THC) Have Divergent Effects on Short-Term Spatial Memory in Young, Healthy Adults

Mäkelä

Wakeley

Gijsman

et al. 2005

Neuropsychopharmacol

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Evidence suggests that manipulating spatial information within working memory depends upon a circuitry organized around the prefrontal cortex (PFC) and the activity of the catecholamine systems. Other evidence attests to the effects of D-9 tetrahydrocannabinol (THC) on short-term spatial memory function, most probably involving CB 1 receptor activity within hippocampal circuitries. At the current time, there have been no systematic studies of the effects of THC on spatial working memory in human subjects using tasks known to depend upon frontotemporal neural circuitries. We examined the effects of a single sublingual 5 mg dose of THC on a test of spatial working memory (requiring active manipulation of remembered spatial information for the management of future behavior) and a test of spatial span (requiring only the reproduction of sequences of previously presented spatial cues). In all, 19 healthy adults were administered 5 mg THC and placebo in a double-blind, placebo-controlled, within-subject, crossover design. Male participants performed more accurately than female participants. THC significantly enhanced spatial working memory performance of female participants. By contrast, male and female participants produced more intrusion errors during performance of the Spatial Span task. These results suggest that THC has relatively complex effects on spatial memory in human subjects, perhaps reflecting altered CB 1 receptor activity within frontotemporal circuits or altered activity of mesocortical dopaminergic pathways in PFC areas associated with spatial memory.

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Health aspects of cannabis

Cited by 204 publications

References 0 publications

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

L-type channel inhibition by CB1 cannabinoid receptors is mediated by PTX-sensitive G proteins and cAMP/PKA in GT1-7 hypothalamic neurons

Association study of the CNR1 gene exon 3 alternative promoter region polymorphisms and substance dependence

Low Doses of Δ-9 Tetrahydrocannabinol (THC) Have Divergent Effects on Short-Term Spatial Memory in Young, Healthy Adults

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