You now how you feel when you smoke that fine bud, but did you ever want to dig deeper…like really geek out on what it does? Well here you go with a little help from “Progress in Neurobiology”.
Cannabinoids have a long history of consumption for recreational and medical reasons. The primary active constituent of the hemp plant Cannabis sativa is Δ9-tetrahydrocannabinol (Δ9-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 Δ9-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 densities 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.
To take it one step further for you deep left brain peeps:
Abbreviations:
AM404,N-(4-hydroxyphenyl)arachidonylamide
cAMP,Adenosine 3′:5′-cyclic monophoshate
CRF,Corticotropin releasing factor
EC50,Half-maximally effective concentration
GABA,γ-Aminobutyric acid
IBMX,3-Isobutyl-1-methyl-xanthine
IC50,Half-maximally inhibitory concentration
LTP,Long-term potentiation
MAP kinase,Mitogen-activated protein kinase
NMDA,N-Methyl-d-aspartate
[35S]GTPγS,5′-[γ-[35S]thio]-triphosphate
SR1417116,N-Piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorphenyl)-4-methyl-3-pyrazole-carboxamide
SR144528,N-[(1S)-endo-1,3,3-trimethyl-bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-1(4-methylbenzyl)-pyrazole-3-carboxamide
Δ9-THC,Δ9-Tetrahydrocannabinol
TNFα,Tumor necrosis factor α
VTA,Ventral tegmental area
WIN55 212-2,R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolol[1,2,3-de]-1,4-benzoxazinyl]-(1-naphtalenyl)methadone
Ok, ready to kiss that CB-1 receptor after all that? I know I am.
The important thing is to work with professionals that know their stuff…and Stinky Leaf has the most knowledgeable as well as downright friendly budtenders on the planet. They will know how to Rock your CB-1 receptor like never before!