Cocaine Subject

Possession and supply illegal except by Home Office Licence Drugs of high abuse potential with medicinal use, opiates and major stimulants, for example amfetamines and cocaine Subject to full controlled drug requirements under the law Drugs of lesser abuse potential with medicinal use for example minor stimulants and barbiturates Subject to special prescription requirements, but not other requirements under the law Anabolic steroids and related hormones Most benzodiazepines and zolpidem Subject to minimal control requirements Sale and supply and possession without a prescription for personal use an offence... 

Other Substances. Driving under the influence of alcohol cases are compHcated because people sometimes consume alcohol with other substances (11—13). The most common iUicit substances taken with alcohol are marijuana and cocaine (see Table 1) (14). In combination with alcohol, some dmgs have an additive effect. When a blood or urine alcohol sample is tested for alcohol and the result is well below the legal concentration threshold yet the test results are not consistent with the arresting officers observation that the subject was stuporous, further toxicological tests for the possible presence of dmgs are indicated. 

Nicotine differs from cocaine in that it is powerfully reinforcing in the absence of subjective euphoria. The high incidence of cancerogenicity associated with longterm tobacco use is associated with compounds other than nicotine that are also contained in tobacco. Main... 

Seecof R, Tennant FS Subjective perceptions to the intravenous rush of heroin and cocaine in opioid addicts. Am J Drug Alcohol Abuse 12 79—87, 1987 Sees KL, Delucci KL, Masson C, et al Methadone maintenance vs. 180-day psycho-socially enriched detoxification for treatment of opioid dependence a randomized controlled trial. JAMA 283 1303-1310, 2000 Sells SB Treatment effectiveness, in Handbook on Drug Abuse. Edited by Dupont RE, Goldstein A, O Donnell J. Washington, DC, U.S. Government Printing Office, 1979, pp 105-118... 

George TP, Chawarski MC, Pakes J, et al Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects a preliminary trial. Biol Psychiatry 47 1080-1086, 2000... 

Sevarino KA, Oliveto A, Kosten TR Neurobiological adaptations to psychostimulants and opiates as a basis of treatment development. Ann N Y Acad Sci 909 51 —87,2000 Silberman EK, Reus VI, Jimerson DC, et al Heterogeneity of amphetamine response in depressed patients. AmJ Psychiatry 138 1302—1307, 1981 Sofuoglu M, Brown S, Babb DA, et al Depressive symptoms modulate the subjective and physiological response to cocaine in humans. Drug Alcohol Depend 63 131-137, 2001... 

Uslaner J, Kalechstein A, Richter T, et al Association of depressive symptoms during abstinence with the subjective high produced by cocaine. Am J Psychiatry 156 1444-1446, 1999... 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Kantak and Miczek 1986). Amphetamine and cocaine, as well as dopaminergic agonists, increase further the already high levels of defensive responses in aggregated rats undergoing withdrawal from opiates, leading in extreme cases to the death of the subjects (Lai et al. 1971 Puri and Lai 1973). 

Javaid, J.I. Fischman. M.W. Schuster, C.R. Dekirmenjian, H. and Davis, J.M. Cocaine plasma concentration Relation to physiological and subjective effects in humans. Science 202 227-228, 1978. 

Figure 5.1 Visualization of the distribution of the DA transporter, D3 receptor, and K2-opioid receptor in the human brain of a drug-free control subject and a representative cocaine overdose victim. (A, B) The DA transporter was measured using [3H]WIN 35,428 (2 nM) as described previously. (C, D) The D3 receptor was measured using [3H]-(+)-7-OH-DPAT (1 nM) in the presence of GTP (300 m/W) to enhance the selective labeling of the D3 receptor subtype over the D2 receptor subtype as described previously. (E, F) The K2-opioid receptor subtype was measured using [125l]IOXY on tissue sections pretreated with BIT and FIT to occlude binding to the p- and 8-opioid receptors, respectively.

The safety of the cocaine vaccine TC-CD in former cocaine abusers has been evaluated in a Phase I clinical trial, and it was determined that the vaccine was well tolerated with dose-related increases in antibody levels.65 Two Phase II clinical trials have now been conducted.66,67 The vaccine was again well tolerated and subjects reported a reduction in cocaine s reinforcing effects. The antibody levels were detectable after the second dose, peaked at 8 to 12 weeks, and remained elevated for up to 6 months preliminary findings indicated a negative association between antibody level and cocaine use. Other anti-cocaine vaccines in development include a blocking antibody (ITAC-cocaine) and a monoclonal catalytic antibody (15A10). 

Streeter C.C., Hennen J., Ke Y. et al. Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment. Psychopharmacology (Berlin). 1, 2005. 

---