The effects of cannabinoids on the brain

The effects of cannabinoids on the brain Cannabinoids have a long history of consumption for recreational and medical reasons. The primary active constituent of the hemp plant Cannabis sativa is Δ 9 -tetrahydrocannabinol (Δ 9 -THC). In humans, psychoactive cannabinoids produce euphoria, enhancement of sensory perception, tachycardia, antinociception, difficulties in concentration and impairment of memory. The cognitive deficiencies seem to persist after withdrawal. The toxicity of marijuana has been underestimated for a long time, since recent findings revealed Δ 9 -THC-induced cell death with shrinkage of neurons and DNA fragmentation in the hippocampus. The acute effects of cannabinoids as well as the development of tolerance are mediated by G protein-coupled cannabinoid receptors. The CB1 receptor and its splice variant CB1A, are found predominantly in the brain with highest densitities in the hippocampus, cerebellum and striatum. The CB2 receptor is found predominantly in the spleen and in haemopoietic cells and has only 44% overall nucleotide sequence identity with the CB1 receptor. The existence of this receptor provided the molecular basis for the immunosuppressive actions of marijuana. The CB1 receptor mediates inhibition of adenylate cyclase, inhibition of N- and P/Q-type calcium channels, stimulation of potassium channels, and activation of mitogen-activated protein kinase. The CB2 receptor mediates inhibition of adenylate cyclase and activation of mitogen-activated protein kinase. The discovery of endogenous cannabinoid receptor ligands, anandamide ( N -arachidonylethanolamine) and 2-arachidonylglycerol made the notion of a central cannabinoid neuromodulatory system plausible. Anandamide is released from neurons upon depolarization through a mechanism that requires calcium-dependent cleavage from a phospholipid precursor in neuronal membranes. The release of anandamide is followed by rapid uptake into the plasma and hydrolysis by fatty-acid amidohydrolase. The psychoactive cannabinoids increase the activity of dopaminergic neurons in the ventral tegmental area-mesolimbic pathway. Since these dopaminergic circuits are known to play a pivotal role in mediating the reinforcing (rewarding) effects of the most drugs of abuse, the enhanced dopaminergic drive elicited by the cannabinoids is thought to underlie the reinforcing and abuse properties of marijuana. Thus, cannabinoids share a final common neuronal action with other major drugs of abuse such as morphine, ethanol and nicotine in producing facilitation of the mesolimibic dopamine system. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Progress in Neurobiology Elsevier

The effects of cannabinoids on the brain

Progress in Neurobiology, Volume 58 (4) – Jul 1, 1999

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Publisher
Elsevier
Copyright
Copyright © 1999 Elsevier Science Ltd
ISSN
0301-0082
DOI
10.1016/S0301-0082(98)00087-2
Publisher site
See Article on Publisher Site

Abstract

Cannabinoids have a long history of consumption for recreational and medical reasons. The primary active constituent of the hemp plant Cannabis sativa is Δ 9 -tetrahydrocannabinol (Δ 9 -THC). In humans, psychoactive cannabinoids produce euphoria, enhancement of sensory perception, tachycardia, antinociception, difficulties in concentration and impairment of memory. The cognitive deficiencies seem to persist after withdrawal. The toxicity of marijuana has been underestimated for a long time, since recent findings revealed Δ 9 -THC-induced cell death with shrinkage of neurons and DNA fragmentation in the hippocampus. The acute effects of cannabinoids as well as the development of tolerance are mediated by G protein-coupled cannabinoid receptors. The CB1 receptor and its splice variant CB1A, are found predominantly in the brain with highest densitities in the hippocampus, cerebellum and striatum. The CB2 receptor is found predominantly in the spleen and in haemopoietic cells and has only 44% overall nucleotide sequence identity with the CB1 receptor. The existence of this receptor provided the molecular basis for the immunosuppressive actions of marijuana. The CB1 receptor mediates inhibition of adenylate cyclase, inhibition of N- and P/Q-type calcium channels, stimulation of potassium channels, and activation of mitogen-activated protein kinase. The CB2 receptor mediates inhibition of adenylate cyclase and activation of mitogen-activated protein kinase. The discovery of endogenous cannabinoid receptor ligands, anandamide ( N -arachidonylethanolamine) and 2-arachidonylglycerol made the notion of a central cannabinoid neuromodulatory system plausible. Anandamide is released from neurons upon depolarization through a mechanism that requires calcium-dependent cleavage from a phospholipid precursor in neuronal membranes. The release of anandamide is followed by rapid uptake into the plasma and hydrolysis by fatty-acid amidohydrolase. The psychoactive cannabinoids increase the activity of dopaminergic neurons in the ventral tegmental area-mesolimbic pathway. Since these dopaminergic circuits are known to play a pivotal role in mediating the reinforcing (rewarding) effects of the most drugs of abuse, the enhanced dopaminergic drive elicited by the cannabinoids is thought to underlie the reinforcing and abuse properties of marijuana. Thus, cannabinoids share a final common neuronal action with other major drugs of abuse such as morphine, ethanol and nicotine in producing facilitation of the mesolimibic dopamine system.

Journal

Progress in NeurobiologyElsevier

Published: Jul 1, 1999

References

  • Functional characteristics of the midbrain periaqueductal gray
    Behbehani, M.M
  • Cannabinoid receptor-regulated cyclic AMP accumulation in the rat striatum
    Bidaut-Russell, M; Howlett, A.C
  • Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain
    Bidaut-Russell, M; Devane, W.A; Howlett, A.C
  • Cannabinoid receptor agonists inhibit Ca current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism
    Caulfield, M.P; Brown, D.A
  • Cannabis and brain function
    Court, J.M
  • Cannabinoids modulate potassium current in cultured hippocampal neurons
    Deadwyler, S.A; Hampson, R.E; Bennett, B.A; Edwards, T.A; Mu, J; Pacheco, M.A; Ward, S.J; Childers, S.R
  • An assessment of the role of opioid receptors in the response to cannabimimetic drugs
    Devane, W.A; Spain, J.W; Coscia, C.J; Howlett, A.C
  • Role of MAP kinase in neurons
    Fukunaga, K; Miyamoto, E
  • Comparative effects of alcohol and marijuana on mood, memory, and performance
    Heishman, S.J; Arasteh, K; Stitzer, M.L
  • Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes
    Henry, D.J; Chavkin, C
  • Endogenous opioid systems and alcohol addiction
    Herz, A
  • Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells
    Levenes, C; Daniel, H; Soubrié, P; Crepel, F
  • Cannabinoid receptor-mediated inhibition of the rat tail-flick reflex after microinjection into the rostral ventromedial medulla
    Martin, W.J; Tsou, K; Walker, J.M
  • Selective vulnerability in Huntington's disease: preferential loss of cannabinoid receptors in lateral globus pallidus
    Richfield, E.K; Herkenham, M
  • Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat
    Sañudo-Peña, M.C; Walker, J.M
  • Cannabinoid effects in basal ganglia in a rat model of Parkinson's disease
    Sañudo-Peña, M.C; Patrick, S.L; Khen, S; Patrick, R.L; Tsou, K; Walker, J.M
  • Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system
    Schatz, A.R; Lee, M; Condie, R.B; Pulaski, J.T; Kaminski, N.E
  • Intrastriatal injection of cannabinoid receptor agonists induced turning behavior in mice
    Souilhac, J; Poncelet, M; Rinaldi-Carmona, M; Le Fur, G; Soubrie, P
  • Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons
    Twitchell, W; Brown, S; Mackie, K
  • Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease
    Volicer, L; Stelly, M; Morris, J; McLaughlin, J; Volicer, B.J

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