lipophilic THC very very soluble hydrocarbons on the tail 20 30 hour half life injection and smoking has higher peak than oral relaxation euphoria decrease reaction time increase hunger memory inhibition Behavioral Effects Decrease in cognition perceptional slowness slow reaction time decrease learning and memory Giddiness Hunger Panic Hallucinations acute psychosis 50 60 have at lease one anxiety experience Sympathetic activator increase heart rate panic caused Precipitate psychosis at at risk individuals Medicinal Uses analgesic decrease pain eating stimulant anti inflammatory adult disorders could be eased Sativex oromucosal spray of THC and CBD approval in Canada 2005 for neuropathic pain MS and cancer Acomplia rimonabant is selective CB1 endocannabinoid receptor antagonist approve Europe 2006 removed 2008 anti smoking and reduced weight with smoking cessation Pharmocotherapies Anti Pain Anti inflammatory appetite inducer Anti obesity marijuana addiction severe depression increase MS 2 Receptors CB1 brain CNS striatum hippocampus substantia nigra VTA cerebellum cerebellum motor effects timing substantia nigra dopamine release reward reinforce movement hippocampus memory CB2 immune system microglia intestinal immune in PNS marijuana one of the safest drugs to take Endocannabinoids anandamine 2 AG fatty acids can t be packaged in vesicles because they will dissolve through no storing just in the axon terminals the are made on demand can t be stored precursors are fatty acids that are part of the cell membrane lipid bilayer synthesis activated by Ca synthesizing enzymes are phospholipases there is an active cell membrane transporter do not need the transporter except for speed metabolized by FAAH anandamine and MAGL 2AG retrograde transport going backwards from postsynaptic to presynaptic Figure 14 12 Fear Conditioning tone and a shock is presented marijuana effects the fear extinction less pain less fear tone is associated with absence of shock so is no longer afraid extinction its new learning during extinction cannabinoids released in the amygdala but not PFC In other types of learning if you give a cannabinoid it has a detrimental effect on learning Endogenous and exogenous THC cannabinoids on GABA and glutamate release endogenous cannabinoids facilitate extinction learning 2AG released receptors on the presynaptic end maybe they do not get up to there unless there is really strong learning leads to increase learning anti pain in the mean time the GABA neurons are effected they decrease so cell is excited which more volume of endogenous cannabinoids more chance to get to the presynaptic because the ones in the post synaptic are saturated exogenous cannabinoids inhibit learning marijuana increases heart rate reduced by antagonist in squirrel monkey THC self administration Probability of initiating marijuana 17 high school into college after 25 it lessens and lessens Trajectories of marijuana use 10 population are chronic users Withdrawal similar to nicotine withdrawal anxiety depression irritability sleep problems decreased appetite restlessness agitation insomnia nausea cramping takes a few weeks to resolve Treatment does not work too well Probability of Developing Psychosis in heavy cannabis users predisposed genetic factors people with the COMT gene polymorphism dopamine and NE breakdown Val Val Genotype very high increased rate of schizophrenia if cannabis use Val met genotype mid met met genotype low schizophrenia