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{"project":"2_test","denotations":[{"id":"24069004-16055773-41849049","span":{"begin":427,"end":429},"obj":"16055773"},{"id":"24069004-14990863-41849050","span":{"begin":431,"end":434},"obj":"14990863"},{"id":"24069004-8508730-41849051","span":{"begin":808,"end":811},"obj":"8508730"},{"id":"24069004-7938127-41849052","span":{"begin":1092,"end":1095},"obj":"7938127"},{"id":"24069004-16290108-41849053","span":{"begin":2216,"end":2219},"obj":"16290108"},{"id":"24069004-10681113-41849054","span":{"begin":3310,"end":3312},"obj":"10681113"},{"id":"24069004-16055773-41849055","span":{"begin":3926,"end":3928},"obj":"16055773"},{"id":"24069004-20525029-41849056","span":{"begin":4241,"end":4243},"obj":"20525029"}],"text":"Effect of exogenous cannabinoids on psychostimulant reward\nAs mentioned previously (see The Endocannabinoid System), an intriguing characteristic of psychostimulants abuse is the concurrent consumption of cannabis. Parallel to studies on the long-term effects of cannabis exposure on subsequent psychostimulant use, researchers also examined the acute rewarding effects of cannabis use on concurrent psychostimulant addiction (91, 222). However, studies aimed at investigating such interactions are sparse. Conflicting results from Foltin et al. and Lukas et al. provide evidence that cannabinoids modulate cocaine-mediated euphoric actions. First, data from Foltin and colleagues show that human volunteers who smoked cannabis prior to intravenous cocaine experience a prolongation of the “high” sensation (248). Second, a study from Lukas and colleagues reveals that smoking Δ9-THC, 30 min prior to intranasal cocaine decreases the latency to onset of cocaine-induced euphoria significantly, from 1.87 to 0.53 min, as well as the duration of cocaine-induced dysphoria, from 2.1 to 0.5 min (249). Interestingly, when both drugs are administered concomitantly, no changes are observed in cocaine- and Δ9-THC-induced positive subjective properties. Furthermore, Δ9-THC increases the peak plasma levels and bioavailability of cocaine considerably. This increase might be the result of Δ9-THC-induced vasodilation of the nasal mucosa which, in turn, reduces cocaine-induced vasoconstriction, thereby increasing cocaine’s absorption. In addition, the discrepancies between these two studies might be also due to pharmacodynamic mechanisms including differences in cocaine absorption or in the ratio of CBD/Δ9-THC levels found in the type of cannabis used for each study.\nUsing fMRI technology combined with script-guided imagery paradigm in which subjects imagined being in a real-life stressful situation, Rajita Sinha’s group found that cannabis abuse contributed to stress-induced blood-oxygen-level-dependent (BOLD) contrast in a group of cocaine-dependent individuals. More specifically, cannabis consumption decreases emotional stress cue-induced frontal and cingulate activation in cocaine-dependent individuals (247). These findings suggest an abnormal cognitive control mechanism during affective processing in association with heavy cannabis use. An important caveat to consider in the latter study is that cocaine-dependent individuals were abstinent for several weeks prior to the neuroimagery session and were not current users of cannabis. Thus the study did not allow to examine the acute effect of cannabis on neural and behavioral responses. However, the fact that this cannabis-induced alteration in stress-response can be translated to cocaine craving and relapse vulnerability has definitely piqued further interest, and initial data on this matter already exists. Indeed, the effects of cannabis consumption on abstinence and relapse to cocaine use have been provided in a study from Labigalini and colleagues, in which 25 cocaine-crack dependent individuals reported to smoke cannabis in order to get relief from abstinence mediated-cocaine-withdrawal symptoms. From this sample, 68% of addicts achieved crack-cocaine cessation while using cannabis during the 9 months duration of the study (90). However, the self-reported nature of this study and its limited duration suggest cautiousness in interpreting its outcome. In a more recent study, Aharonovich et al. drew opposite conclusions on the consequences of smoking cannabis on cocaine relapse. In this study, researchers investigated whether cannabis use after the discharge of 144 drug-addicts from inpatient treatment program could help them to maintain abstinence and thereby preventing relapse to cocaine use. Results from this study suggest that smoking cannabis reduced the achievement of sustained remission and increased relapse to cocaine use (91) (see Table 1). Surprisingly, a study from Jutras-Aswad et al. supports the assumption that irregular cannabis use increases risky behaviors (syringe sharing) of cocaine and opioid users, as opposed to regular cannabis use, suggesting a complex dose-effect relationship between cannabis and addictive behaviors (22). The possibility that cannabis use by recently abstinent cocaine-dependent individuals influences relapse to drug and other related behaviors remains poorly documented."}

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