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Transcript
ADDICTION Cannabinoid Professor Suleiman Olimat What is addiction? (Latin) addictus---attached to something, positive. Today alcoholism called a “brain disease”or bad habit or sin. Leading assumption of the text: Addiction is the key, not the substance or behavior Addiction defined by researchers as “a bad habit,” “a brain disease,” “helplessness,” “a problem of motivation” Definitions Addiction—pattern of compulsive use. Has physical, psychological, social aspects. Emphasis on process rather than outcome. The Diagnostic and Statistical Manual of Mental Disorders (DSM ( Changes to DSM in new edition: no longer dichotomy between abuse and dependence Addiction now the preferred term instead of dependence. Addiction now seen as a continuum. Substance use disorder requires 2 of following: tolerance withdrawal problems use more than intended reduced involvement inability to stop excessive spending or effort to obtain continued use The question is often asked: Why would anyone addict to drugs? Research has shown that people generally take drugs to either feel good (i.e., sensation seekers, or anyone wanting to experiment with feeling high or feeling different) or to feel better (i.e., self-medicators, or individuals who take drugs in an attempt to cope with difficult problems or situations, including stress, trauma, and/or to lessen anxiety, fears, depression, or hopelessness). Why people taking Drugs? Why Do People Take Drugs in The First Place? They like what it does to their brains To Feel Good To Feel Better Image courtesy: Vivian Felsen From being an addict to being a poet. Dependence Physical Dependence: Withdrawal of drug produces physical symptoms. Body needs the drug for normal physiological function Psychological Dependence: Cravings for a drug, overcome by the desire to have a drug. Cannabinoid Structure of THC and synthetic analogs Lipophilic side chain Most potent analog: 100s times more potent than THC Commonly used terms • Cannabis is the preferred general term. • Other terms: marijuana, ganga, mull, grass, hash, pot, weed, dope • Types of cannabis, in increasing strength – Leaf << Head << Oil/resin • Diverse methods of smoking – joint = cigarette of cannabis, typically 0.5g – cone: smoked via a water pipe (bong), typically 0.25g – vaporisers (increased ammonia levels via this method) Why do people use cannabis? • To experience euphoria or perceptual distortions • Because others do so • To relieve mental symptoms – negative symptoms of schizophrenia – anxiety • To relieve physical symptoms – Eg. nausea, anorexia, cancer & HIV The Cannabis High Described Gives sensation of euphoria, relaxation, sexual arousal. 1sttime users may experience nothing (experts say they must learn to appreciate the effects) -Marijuana tends to inhibit aggression and accentuate caution as opposed to alcohol -Marijuana causes time expansion (over estimation of time elapsed) -Workers say that smoking marijuana help them to work harder Typical effects of cannabis • Mental effects – Euphoria, relaxation and wellbeing – Increased appetite (‘munchies’) – Talkativeness, disinhibition • Physical effects – Vasodilator (systemic and portal) – Bronchodilation (short-term effect only) • Highly variable – Many people dislike it and discontinue use – Influenced by surroundings Cannabinoid Receptors G protein-coupled, with seven transmembrane regions • CB1 Brain, fat cells, liver, duodenum, muscle • CB2 lymphocytes>macrophages>cytokines Mode of cannabis action • Two specific cannabinoid receptors – CB1 - brain and peripheral tissues – CB2 - immune system • Linked to G-proteins with diverse downstream signalling pathways • Euphoria results from stimulation of mesolimbic dopaminergic neurons, like other drugs of abuse Cannabinoid CB1 and CB2 Receptors Characteristics of CB1 and CB2 Receptors • • • • • • Both densely distributed throughout the body CB1 highly enriched in central nervous system Located on axon terminals Mediate retrograde signaling (Dendrite → Axon) G-protein coupled CB2 highly enriched in periphery – Especially in immune system • CB2 also in brain and CNS – Fewer than CB1; ~ Same density as μ opioid – Nonetheless, CB2s modulate neural signaling CB1 and CB2 • Here is a picture of a synapse containing the endogenous cannabinoid system. The CNS contains CB1 receptors and natural neurochemicals such as anandamide and 2-AG. • Presynaptic neuron (releasing glutamate or GABA) • Postsynaptic neuron and receptors • Glutamate acting on glutamate receptor proteins nested in postsynaptic membrane • Presynaptic CB1 receptor - many CB1 receptors appear to be presynaptic. That is, in many cases this system acts to modulate the release of other neurotransmitters eg.glutamate. That is, act to inhibit the release of other neurochemicals. • A new study published in the prestigious journal Nature has shown that endogenous cannabinoid are synthesised postsynaptically, when the postsynaptic cell receives a large influx of calcium ions, and then travel backwards to act on presynaptic cannabinoid autoreceptors to inhibit the release of neurotransmitters GABA or glutamate. Neurotransmitter Receptor Influences nt release Neurotransmitter Receptor Post-synaptic release of endog. cannabinoid Annandamide (arachidonyl-ethanolamid) 2-Arachidonoyl - glycerol (2AG) more abundant, less potent Endocannabinoids Both Δ9-THC, the psychoactive component of Cannabis sativa, and anandamide, an endogenous neurotransmitter in our brain, bind o the same cannabinoid receptor CB1 receptor summary • Abundantly expressed throughout the brain • Majority on axons and synaptic terminals • CB1 activation inhibits synaptic transmission Endocannabinoids: Bind CB1 > CB 2 Drugs Can be Chemical Imposters (THC mimics a natural brain chemical) Brain’s Chemical Drug Anandamide THC Effects on Reproduction There is not evidence of long term reproductive problems from cannabis use, yet hormonal changes do occur. Males: • Reduces level of testosterone (still within normal levels) • Reduces sperm count (10 joints/day, effect disappears when use stopped) • Changes in shape and morphology of sperm • Effects of THC can be estrogen-like producing breast development (gynecomastia). Females: • Reduction in luteinizing hormone, necessary for egg implantation into the uterus. (Not seen in regular users – implies tolerance). • Reduction of prolactin levels (associated with increased release of dopamine in the hypothalamus), effecting lactation. Effects on Cognition There is evidence that long term use may lead to deficits in learning memory and attention. However, it is unknown how long these deficits may persist after abstinence from the drug. Significant prior usage may reduce the adverse cognitive effects of acute marijuana exposure. This has led to the hypothesis that behavioral (“cognitive”) tolerance develops in heavy marijuana smokers. Effects of Heavy Marijuana Use on Attention, Learning, & Memory in Undergraduates Researchers compared 65 "heavy users," (smoked a median of 29 of the past 30 days), and 64 "light users," (smoked a median of 1 of the past 30 days). After 19-24 hours of abstinence from marijuana and other illicit drugs and alcohol, the undergraduates were given several standard tests measuring aspects of attention, memory, and learning. Heavy marijuana users made more errors and had more difficulty sustaining attention, shifting attention to meet the demands of changes in the environment, and in registering, processing, and using information. However, the question remains open as to whether this impairment is due to a residue of drug in the brain, a withdrawal effect from the drug, or a frank neurotoxic effect of the drug? A motivational Syndrome. Recent studies have found that users of moderate amounts of marijuana show no personality disturbances, but heavy users were characterized as suffering from apathy, dullness, lethargy, and impairment of judgment. However, heavy users were defined as people who smoked 17-200 marijuana cigarettes per day! Does marijuana lead to ? There is evidence that cannabis use is correlated with degradation in mental health, especially in those with a predisposition to mental illness. However, it is uncertain whether cannabis use is a cause, contributing factor, associated social phenomenon, or type of self-medication. In North Africa and India, higher incidence of psychiatric problems associated with THC are reported. Withdrawal Symptoms Marijuana addiction is also linked to a withdrawal syndrome that can make it hard to quit. Symptoms include: • • • • • irritability, sleeping difficulties, craving, anxiety, and increased aggression. Warning Marijuana is illegal in most places Marijuana is, in general, much less dangerous than it is made out to be, and certainly less harmful than legal drugs like tobacco and alcohol. It is impossible die from marijuana, unlike most other illegal drugs and many legal ones. Most of the supposed scientific evidence for brain damage, infertility, etc. have been disproven.