Addictive cannabinoids

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If opiates are such addictive and potentially lethal compounds, why does the body respond to them As with the cannabinoids (Chapter 7), it has been discovered that the body and brain possess numerous opiate-specific receptor sites. As many as nine receptor subtypes have been identified, with three of them being the most important p (mu), k (kappa) and 8 (delta). The finding that the distribution of opiate receptors did not parallel the distribution of any known neurotransmitter prompted the search for and identification of a number of endogenous compounds specific to these receptors. These enkephalins and endorphins are manufactured within the brain and other body systems (especially the gut and intestines) and form the body s natural response to pain. They appear to be produced in bulk chains of amino acids called polypeptides , with each active neurotransmitter being composed of around five amino acid molecules. These active neurotransmitters are subsequently cleaved from the larger polypeptides at times of demand for example, it has been demonstrated that the plasma levels of these active compounds rise during childbirth, traumatic incidents and vigorous physical exercise. 

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Box 11.2 Addiction to chocolate, brain cannabinoids and arachidonic acid... 

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The classification of NMDA antagonists as nonaddictive drugs was based on early assessments, which, in the case of PCP, have recently been questioned. In fact, animal research shows that PCP can increase mesolimbic dopamine concentrations and has some reinforcing properties in rodents. Concurrent effects on both thalamocortical and mesolimbic systems also exist for other addictive drugs. Psychosis-like symptoms can be observed with cannabinoids, amphetamines, and cocaine, which may reflect their effects on thalamocortical structures. For example, cannabinoids, in addition to their documented effects on the mesolimbic dopamine system, also enhance excitation in cortical circuits through presynaptic inhibition of GABA release. 

Children of women addicted to opiates, cannabinoids or alcohol or chronically treated with benzodiazepines during pregnancy are often born with withdrawal symptoms, and/or show retarded behavior and various other abnormalities when growing up. Therefore, relatively extensive research has been performed in this field. Animal studies have shown that behavioral abnormalities found in laboratory animals treated prenatally with these substances extended well into adulthood (ref. 8). For instance, children... 

Urigiien, L., Perez-Rial, S., Ledent, C., Palomo, T., and Manzanares, J. (2004). Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors. Neuropharmacology 46, 966-973. Vandrey, R. G., Budney, A. J., Moore, B. A., and Hughes, J. R. (2005). A cross-study comparison of cannabis and tobacco withdrawal. Am.J. Addict. 14, 54-63. 

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Today, scientists continue to try to unravel the biological mechanisms by which cannabinoids relieve pain, with hopes that one day a synthetic cannabinoid drug will be produced that can be legally prescribed to alleviate pain and suffering in people with AIDS, cancer, and other illnesses that cause chronic pain. At the same time, scientists hope that this new cannabinoid pain reliever will be free of the negative effects of marijuana, which include intoxication and addiction. 

Bals-Kubik R, Ableitner A, Herz A, Shippenberg TS (1993). Neuroanatomical sites mediating the, motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. J Pharmacol Exp Ther 264 489-495 Maldonado R, Rodriguez de Fonseca F (2002) Cannabinoid addiction behavioral models and neural correlates. J Neu-rosci 22 3326-3331... 

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