Morphine Cannabinoids

The toxicological or cumulative effect of illicit drugs on the ecosystems has not been studied yet. Moreover, their fate and transport in the environment is to a big extent still unknown. Due to their physical-chemical properties (octanol-water partition coefficient, solubility, etc.) some of them, such as cannabinoids, are likely to bioaccumulate in organisms or concentrate in sediments whereas the rest, much more polar compounds, will tend to stay in aqueous environmental matrices. However, continuous exposure of aquatic organisms to low aquatic concentrations of these substances, some of them still biologically active (e.g., cocaine (CO), morphine (MOR) and MDMA) may cause undesirable effects on the biota. 

Fig. 1 Concentrations reported for opiods and cannabinoids in surface water of different European countries. MOR morphine Nor-MOR nor-morphine 6ACM 6-monoacetyl morphine HER heroin MET methadone EDDP 2-ethylidene-l,5-dimethyl-3,3 diphenylpyrrolidine THC A9-tetrahydro-cannabinol THC-COOH 11-nor 9-carboxy-THC N/A Values not availabe, not measured...

Lichtman AH, Sheikh SM, Loh HH, et al Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther 298 1007—1014, 2001... 

Peterson PK, Gekker G, Hu S, Cabral G, Lokensgard JR (2004) Cannabinoids and morphine differentially affect HIV-1 expression in CD4(-t) lymphocyte and microglial ceU cultures. J Neuroimmunol 147(1-2) 123-126... 

CP-55,940 (8.5) was developed during the search for novel analgesics [146]. Although it is more potent than morphine it was never approved. Nevertheless, in its tritium-labeled form it became a very important tool for research and helped in the first identification of the cannabinoid receptor. 

Contrary to other studies, 6ACM and THC presented 100% removal in this study, but due to their low frequency of detection in raw wastewaters and then-absence in treated wastewaters (see Figs. 2 and 5). This fact also affects the overall satisfactory removal of opioids (88%) and cannabinoids (79%). However, removal of morphine, the opioid most frequently detected in wastewaters ranged between 46 and 100%, variability also observed by other authors. In the case of cannabinoids, removals reported are very diverse. The average poor removal observed for THC-COOH in the investigated WWTPs from the Ebro River basin (48%) results from occasionally higher concentrations of this analyte in treated wastewaters compared to raw wastewaters. This finding has also been reported in other studies [7, 19]. 

Synergistic effects are produced by co-administration of morphine and cannabinoids (Pugh et al. 

Hamann SR, Martin WR. (1994). Hyperalgesic and analgesic actions of morphine, U50-488, naltrexone, and (-)-lobeline in the rat brainstem. Pharmacol Biochem Behav. 47(1) 197-201. Hamann W, di Vadi PP. (1999). Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. Lancet 353(9152) 560. 

Welch SP, Stevens DL. (1992). Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. J Pharmacoi Exp Ther. 262(1) 10-18. 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

Some studies have suggested that there may be links between the development of dependence to cannabinoids and to opiates (42). Some of the behavioral signs of rimonabant-induced withdrawal in THC-treated rats can be mimicked by the opiate antagonist naloxone (43). Conversely, the withdrawal syndrome precipitated by naloxone in morphine-dependent mice can be partly relieved by THC (44) or endocannabinoids (45). Rats treated chronically with the cannabinoid WIN55212-2 became sensitized to the behavioral effects of heroin (46). Such interactions can also be demonstrated acutely. Synergy between cannabinoids and opiate analgesics has been described above. THC also facilitated the antinociceptive effects of RB 101, an inhibitor of enkephalin inactivation, and acute administration of THC caused... 

The availability of receptor knockout animals has also helped to illustrate cannabinoid-opioid interactions. CBi receptor knockout mice had greatly reduced morphine self-administration behavior and less severe naloxone-induced withdrawal signs than wild type animals, although the antinociceptive actions of morphine were unaffected in the knockout animals (40). The rimona-bant-precipitated withdrawal syndrome in THC-treated mice was significantly attenuated in animals with knockout of the pro-enkephalin gene (48). Knockout of the p opioid (OP3) receptor also reduced rimonabant-induced withdrawal signs in THC-treated mice, and there was an attenuated naloxone withdrawal syndrome in morphine-dependent CBi knockout mice (49,50). 

Dogrul A, Gul H, Akar A, Yildiz O, Bilgin F, Guzeldemir E (2003) Topical cannabinoid antinociception synergy with spinal sites. Pain 105 11-16 Dogrul A, Seyrek M (2006) Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HTlA and 5-HT2 receptors in the spinal cord. Br J Pharmacol 149 498-505... 

Swanson LW, McKellar S (1979) Distribution of oxytocin-stained and neurophysin-sttiined fibers in the spinal-cord of the rat and monkey. J Comp Neurol 188 87-106 Sweeney MI, White TD, Sawynok J (1987) Involvement of adenosine in the spintd tmtinociceptive effects of morphine and noradrenaline. J Pharmacol Exp Ther 243 657-665 Szabo B (2008) Pharmacology of cannabinoid receptors. Biotrend Rev 2 1—13 Szabo C (2007) Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 6 917-935 Szeto HH (2003) Dynorphin and the hypothalamo-pituitary-adrenal axis during fetal development. Life Sci 73 749-758... 

Electrochemical detectors can be used in the oxidative mode for a wide range of drugs, including cannabinoids, haloperidol, morphine, paracetamol, phenothiazines, salicylic acid, and tricyclic antidepressants. Operation in the reductive mode is more difficult as dissolved oxygen must be removed from the eluent (K. Bratin et al, J. liq. Chromat., 1981,, 1777-1795). Reductive applications include chloramphenicol and benzodiazepines. 

Keywords Cannabinoids Cheniokines Cocaine Cytokines Immunosuppression Morphine Opioids T-helper 1/T-helper 2 (Thl/Th2) A9-tetrahydrocannabinol (A -THC) Tolerance Withdrav al... 

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