Psychoactive drugs, inhibition

Psychoactive drugs can influence neurotransmission at its five different stages (Chapter 2). First, they may modify the biosynthesis of a neurotransmitter. Second, they can increase or decrease their storage within the presynaptic neuron. Third, they may stimulate or inhibit neurotransmitter release from the synaptic bouton. Fourth, they may affect the binding of the neurotransmitters to its receptor. Finally, they can retard the neurotransmitter s inactivation. Some examples of each of these stages will be given below, but it should be noted that many drugs affect several of these processes. 

Many psychoactive drugs act to alter neurotransmitter functions either through effects on their synthesis, metabolism or reuptake or by directly affecting the receptors for naturally occurring compounds. For example, drugs such as prozac increase serotoniner-gic activity by selective serotonin reuptake inhibition (SSRI). 

Murphy DL, Donnelly C, Moskowitz J Inhibition by lithium of prostaglandin El and norepinephrine effects on cyclic adenosine monophosphate production in human platelets. Chn Pharmacol Ther 14 810-814, 1974b Murphy DL, Lake CR, et al Psychoactive drug effects on plasma norepinephrine and plasma dopamine B-hydroxylase in man, in Catecholamines Basic and Clinical Frontiers. Edited by Usdin E, Kopin IJ, Barchas J. Ehnsford, NY, Pergamon, 1979, pp 918-920... 

The screening results showed no significant competitive inhibition of reference target compounds at any of the following sites tested. The receptor sites tested included those effected by most other major psychoactive drugs. 

THC 4 d) and other cannabinoids undergo extensive biotransformation in the body, yielding scores of metabolites, several of which are themselves psychoactive. They are extremely lipid-soluble and are stored in body fat from which they are slowly released. Hepatic drug metabolising enzymes are inhibited acutely but may also be induced by chronic use of crude preparations. 

Delta-9-THC is the main active constituent extracted from Cannabis sativa (Tuner, 1985 in Marijuana 1984, Ed. Harvey, DY, IRL Press, Oxford). Numerous articles have described not only psychotropic effects of cannabinoids but also their influence on the immune function [Hollister L. E., J. Psychoact. Drugs 24 (1992) 159-164]. The majority of in vitro studies have shown that cannabinoids have immunosuppressant effects inhibition of the mitogen induced proliferative responses of T lymphocytes and B lymphocytes [Luo, Y. D. et ah, Int. J. Immuno-pharmacol. (1992) 14,49-56 Schwartz, H. et at., J. Neuroimmunol. (1994) 55,107-115], inhibition of the activity of cytotoxic T cells [Klein et at., J. Toxicol. Environ. Health (1991) 32, 465-477], inhibition of the microbicidal activity of macrophages and of TNF-a synthesis [Arata, S. et at.. Life Sci. (1991) 49, 473-479 Fisher-Stenger et al., J. Pharm. Exp. Then (1993) 267, 1558-1565] and inhibition of the cytolytic activity and the TNFa production of large granular lymphoc3rtes [Kusher et al.. Cell. Immun. (1994) 154, 99-108],... 

Another neurotransmitter system, that is a potential target for psychoactive drugs detected in the environment, is GABA, which is one of the most abundant neurotransmitters in the vertebrate central nervous system and is considered the main inhibitory neurotransmitter. Injections of GABA rapidly increased GTH-II release in goldfish by stimulation of GnRH release and inhibition of the inhibitory DA system66. 

In addition to the psychoactive drugs, various agents with local anesthetic-like properties bind weakly in a Ca +-dependent manner (77). Another agent found to bind in the presence of Ca + and inhibit calmodulin-dependent enzymes is the sulfonamide,... 

Acute and chronic administration of alcohol can inhibit the biotransformation or detoxification of many drugs, such as barbiturates, meprobamate, and amphetamines by liver enzymes. The effect can occur in two opposite ways. Alcohol and cannabinoids effects are additive. Both are CNS depressants. Animal studies indicate that simultaneous administration of alcohol and tetrahydrocannabinol (THC), the psychoactive component of marijuana, increased the tolerance and physical dependence to alcohol. Human studies show that alcohol and THC combination enhanced the impairment of physical and mental performance only, and there is no evidence of any interaction between both drugs. With barbiturates. 

Sativex contains approximately equal proportions of dronabinol and cannabidiol delivered in an oral spray providing an onset of action of only 15-40 minutes with peak effect occurring similarly to the oral drugs. The cannabidiol may decrease psychotropic effects either by competitive inhibition for the CBj receptor site and/or by decreasing the metabolism of dronabinol to 11-hydroxy-A -THC, which may be more psychoactive than A -THC. 

---