Depression cannabinoids

Trettel J, Levine ES (2002) Cannabinoids depress inhibitory synaptic inputs received by layer 2/3 pyramidal neurons of the neocortex. J Neurophysiol 88 534-539... 

Freiman 1, Szabo B (2005) Cannabinoids depress excitatory neurotransmission between the subthalamic nucleus and the globus pahidus, Neurosci 133 305-313 French CL, Irwin RS, Curley FJ, Krikorian CJ (1998) Impact of chronic cough on quahty of life. Arch Intern Med 158 1657-1661... 

Cornelius JR, Salloum IM, EhlerJG, et al Fluoxetine in depressed alcoholics a doubleblind, placebo-controlled trial. Arch Gen Psychiatry 54 700—705, 1997 Cornelius JR, Salloum IM, Haskett RF, et al Fluoxetine versus placebo for the marijuana use of depressed alcoholics. Addict Behav 24 111—114, 1999 Cui S-S, Bowen RC, Gu G-B, et al Prevention of cannabinoid withdrawal syndrome by lithium involvement of oxytocinergic neuronal activation. J Neurosci 21 9867— 9876, 2001... 

Tables 6.8-6.11 illustrate the wide range of C3 side-chain modified A -THC analogues that have been reported in the literature, together with associated in vitro and in vivo data. The affinity of classical cannabinoid analogues for the CBi receptor has been shown to correlate with depression of spontaneous activity and the production of antinociception, hypothermia and catalepsy in mice, and with psychomimetic activity in humans [93]. However, in some cases, there were unexplained differences between the observed trends in binding affinity and the trends in activity in mouse behavioural models. This may point to differences in efficacy among full agonists, partial agonists and antagonists/inverse agonists, or may reflect differences in in vivo metabolism or blood-brain barrier penetration or a combination of these factors.

Electrophysiological responses to cannabinoids are complex. THC produces both CNS excitation and depression in several electrophysiological paradigms (Turkanis and Karler 1981). The effect produced depended on the cannabinoid dosage and paradigm used. In contrast to THC, cannabidiol generated no CNS excitation, and produced either depressant effects or no effects at all. 

Tramposch A, Sangdee C, Franz DN, Karler R, Turkanis SA. (1981). Cannabinoid-induced enhancement and depression of cat monosynaptic reflexes. Neuropharmacology. 20(6) 617-21. Tripathi FIL, Vocci FJ, Brase DA, Dewey WL. (1987). Effects of cannabinoids on levels of acetylcholine and choline and on turnover rate of acetylcholine in various regions of the mouse brain. Alcohol Drug Res. 7(5-6) 525-32. 

Psychiatric patients In manic, depressive, or schizophrenic patients, symptoms of these disease states may be exacerbated by the use of cannabinoids. 

I. 18-1.62), number-needed-to-treat (NNT) was 6 for complete control of nausea relative risk was 1.28 (Cl 1.08-1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles relative risk 2.39 (2.05-2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids high 10.6 (6.86-16.5), NNT 3 sedation or drowsiness 1.66 (1.46-1.89), NNT 5 euphoria 12.5 (3-52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids dizziness 2.97 (2.31-3.83), NNT 3 dysphoria or depression 8.06 (3.38-19.2), NNT 8 hallucinations 6.10 (2.41-15.4), NNT 17 paranoia 8.58 (6.38-... 

Luo, J., J. H. Yin, H. Z. Wu, and Q. Wei. Extract from Fructus cannabis activating calcineurin improved learning and memory in mice with chemical drug-induced dysmnesia. Acta Pharmacol Sin 2003 24(11) 1137-1142. Degenhardt, L., W. Hall, and M. Lynskey. Exploring the association between cannabis use and depression. Addiction 2003 98(11) 1493-1504. Zajicek, J., P. Pox, H. Sanders, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study) multicentre randomised placebo-controlled trial. Lancet 2003 362(9395) 1517-1526. 

Of the specific cannabinoids studied at Edgewood, pharmacologic data are available on DMHP. It was effective in producing sedation in animals at oral doses lower than 0.5 mg/kg. Several doses and routes of administration were studied, up to 1 mg/kg given intravenously. In rats, sedation occurred without initial stimulation in dogs and monkeys, hyperactivity was followed by depression and then, at higher doses, by coma. Motor effects were dramatic, in that animals developed spastic ataxia and showed extremely active deep tendon... 

The tests are designed to predict which of seven categories of drug the suspect may have used (1) CNS depressants, (2) CNS stimulants, (3) cannabinoids, (4) phencyclidine, (5) opioids, (6) hallucinogens, and (7) inhalants. The combination of results from the laboratory analysis of the blood or urine sample and from the 12-step evaluation test will help decide whetherthe defendant was impaired at the time of the stop. 

THC was first isolated from hashish in 1964 by Raphael Mechoulam (1930-) and Yehiel Gaoni at the Weizmann Institute. Mechoulam had obtained 5 kg hashish from Israeli police officials and the earliest scientific work on THC and cannabinoids used this source. In the early 1990s, the specific brain receptors affected by THC were identified. These receptors are activated by a cannabinoid neurotransmitter called arachidonylethanolamide, known as anandamide. Anandamide was named by Mechoulam using ananda, which is the Sanskrit word for ecstasy. Anandamide is thought to be associated with memory, pain, depression, and appetite. THC is able to attach to and activate anandamide receptors. These receptors are actually called THC receptors rather than anandamide receptors because researchers discovered that THC attaches to these receptors before anandamide was discovered. The areas of the brain with the most THC receptors are the cerebellum, the cerebral cortex, and the limbic system. This is why marijuana affects thinking, memory, sensory perception, and coordination. 

Cannabinoids Hashish Marijuana Psychoactive drugs with mixed (stimulant and depressant] activity Smoked possible oral ingestion Initial response euphoria, excitement, increased perception later response relaxation, stupor, dreamlike state Endocrine changes (decreased testosterone in males] and changes in respiratory function similar to chronic ... 

Daniel H, Rancillac A, Crepel F (2004) Mechanisms underlying cannabinoid inhibition of presynaptic Ca2+ influx at parallel fibre synapses of the rat cerebellum. J Physiol 557 159-74 Davies CH, Davies SN, Coflingridge GL (1990) Paired-pulse depression of monosynaptic GABA-mediated inhibitory postsynaptic responses in rat hippocampus. J Physiol 424 513-31 De Camilli P, Greengard P (1986a) Synapsin I a synaptic vesicle-associated neuronal phospho-protein. Biochem Pharmacol 35 4349-57... 

Cannabinoids, Endocannabinoids, and Presynaptic Depression 3.1 Actions of Synthetic Cannabinoids... 

Cannabinoid and endocannabinoid-induced synaptic depression is observed in both the peripheral nervous system and the CNS. Indeed, A9-THC inhibition of transmitter release was first demonstrated in mouse vas deferens (Graham et al. 1974), and further evidence for presynaptic inhibition has been obtained using this preparation (Ishac et al. 1996 Pertwee and Fernando 1996) and in the myenteric plexus (Coutts and Pertwee 1997 Kulkami-Narla and Brown 2000). In addition, anandamide was first characterized as an EC based on its actions in the mouse vas deferens (Devane et al. 1992). Subsequently, CB1 receptor-mediated inhibition of release of several neurotransmitters has been documented in various regions of the PNS (see Szabo and Schlicker 2005 for review). Cannabinoids also inhibit neural effects on contraction in the ileum (Croci et al. 1998 Lopez-Redondo et al. 1997), although it is not clear that this is effect involves direct inhibition of neurotransmitter release (Croci et al. 1998). The CB1 receptor has been localized to enteric neurons, and thus the effect on ileum certainly involves actions on these presynaptic neurons. In addition, anandamide produces ileal relaxation via a non-CBl, non-CB2-mediated mechanism (Mang et al. 2001). 

Huang CC, Lo SW, Hsu KS (2001) Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons. J Physiol 532 731—48 Huang YC, Wang SJ, Chiou LC, Gean PW (2003) Mediation of amphetamine-induced long-term depression of synaptic transmission by CB1 cannabinoid receptors in the rat amygdala. J Neu-rosci 23(32) 10311-20... 

Kahn L, Alonso G, Robbe D, Bockaert J, Manzoni OJ (2001) Group 2 metabotropic glutamate receptors induced long term depression in mouse striatal slices. Neurosci Lett 316(3) 178-82 Kamprath K, Marsicano G, Tang J, Monory K, Bisogno T, Di Marzo V, Lutz B, Wotjak CT (2006) Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes. J Neurosci... 

Kreitzer AC, Malenka RC (2005) Dopamine modulation of state-dependent endocannabinoid release and long-term depression in the striatum. J Neurosci 25(45) 10537—45 Kreitzer AC, Regehr WG (2001) Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto purkinje cells. Neuron 29 717-27 Kreitzer AC, Carter AG, Regehr WG (2002) Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 34 787-96... 

---