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Stimulants: cocaine, amphetamines and party drugs
Published in Berry Beaumont, David Haslam, Care of Drug Users in General Practice, 2021
Increasing use and doses of stimulants can result in a number of psychological effects. Visual or tactile hallucinations may occur. Sometimes users pick at their skin (the ‘cocaine bug’) or crawl round the floor picking up imaginary insects. Some develop automated behaviour, for example repetitively taking a clock apart and putting it back together. Feelings of anxiety, irritability and restlessness may lead on to suspiciousness and paranoid behaviour. Stimulant psychosis is a toxic state characterised by persecutory delusions and hallucinations occurring in a state of high arousal. Reverse tolerance may occur to these effects, with increased sensitisation over time. However, for most chronic users euphoria becomes ever harder to achieve. The majority of chronic stimulant users eventually develop clinical depression in spite of continued use.
Cannabis
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
Some experienced users of cannabis report that instead of becoming tolerant to its effects, they become more sensitive to cannabis after the first few trials.15 There has been a fair amount of speculation as to biochemical mechanisms for this so-called “reverse tolerance” phenomenon.10,73,74 Mechoulam suggested enzyme induction may result in more effective metabolism with repeated exposure.10 This would be consistent with the shorter halflife of THC in the blood of users particularly if cannabis psychoactivity is associated primarily with a metabolite. There is, however, some suggestion that the often cited decreased sensitivity to cannabis on the first few exposures may be folklore with little basis in fact.19,20 If it is a common phenomenon, it can be explained readily on the basis of repeated exposure to low potency marijuana where psychological factors are the primary determinants of the subjective state.16 Shared cultural values and learning are thought to play an important role in determining the interpretation and labeling of the state resulting from smoking cannabis.77 If the “reverse tolerance” is chemically determined, it is remarkable that only sensitivity to psychic effects appears and more traditional tolerance is seen with behavioral and physiologic measures.16,23,78–80
Stimulants
Published in G. Hussein Rassool, Alcohol and Drug Misuse, 2017
Depending on how amphetamines are taken, the effects may be felt in only a few minutes (snorting), almost instantly (injecting) or within 30 minutes (swallowed). The effects of a single dose last for four to eight hours, although the after-effects can last for several days. Chronic users of amphetamines typically snort or resort to drug injection to experience the full intensity effects of the drug with the added risks of infection, vein damage and higher risk of overdose. The use of amphetamine is highly addictive, and, with chronic abuse, tolerance develops very quickly. Repeated amphetamine use can produce “reverse tolerance”, or sensitisation to some psychological effects. Many amphetamine users will repeat the amphetamine cycle by taking more of the drug during the withdrawal. This leads to a very dangerous cycle and may involve the use of other drugs to get over the withdrawal process. Withdrawal, although not physiologically threatening, is an unpleasant experience. How severe and prolonged these withdrawal symptoms are depends on the degree of abuse. Key withdrawal symptoms of amphetamines are presented in Table 10.2.
Kava (Piper methysticum) in the United States: the quiet rise of a substance with often subtle effects
Published in The American Journal of Drug and Alcohol Abuse, 2023
Salma Pont-Fernandez, Marina Kheyfets, Jeffrey M. Rogers, Kirsten E. Smith, David H. Epstein
Kava’s subjective effects were typically described as either mild or imperceptible, and many posts discussed efforts to potentiate them through preparation methods such as refrigerating kava drinks before use. One possible explanation for the reported weakness of kava’s effects is reverse tolerance, mentioned in 4% of posts. Reverse tolerance refers to an increase in response to a substance after consistent use (50). While reverse tolerance has been described for psychostimulants, nicotine, and alcohol (50–55), its occurrence for kava has apparently been mentioned only in anecdotal reports on blog posts (56–58). If it occurs, we do not know whether it reflects a direct pharmacological change or a learned appreciation for kava’s effects.
Non-opioid antinociceptive drugs : risk of respiratory depression and death related to concomitant use of gabapentinoids in addition to opioids
Published in Expert Opinion on Drug Safety, 2023
Marine Tambon, Berenice Montarnal, Marianne Lepetit, Maryse Lapeyre-Mestre
Previous studies in animals investigating the potential of reverse morphine tolerance identified a positive effect with pregabaline (lack of published studies with gabapentin). In Lyndon’s study, to investigate the effect of pregabalin on morphine tolerance, mice previously treated with morphine for 6 days received a unique injection of pregabalin at the same time as the challenge dose of morphine [21]. This pregabalin dose alone produced very little depression of respiration in both naive mice and mice pretreated with morphine. In morphine‐pretreated mice that were injected with pregabalin at the same time as the acute morphine challenge, respiration was depressed significantly. The authors concluded that this observation was consistent with pregabalin reversal of morphine tolerance, which has also been demonstrated with the association of oxycodone and pregabalin in mice [9]. Mice developed tolerance to oxycodone and cross-tolerance to morphine-induced respiratory depression. At doses that do not depress respiration, pregabalin and low-dose ethanol administered simultaneously with the acute morphine challenge were able to reverse oxycodone-induced tolerance, resulting in significant respiratory depression. The authors concluded that reverse tolerance may be mediated by inhibition of Protein Kinase C (PKC), even if there is no evidence to date that pregabalin or gabapentin directly inhibits PKC. Actually, these findings in animal studies and congruent results of observational data in different clinical contexts suggest that pregabalin is at high risk for patients exposed to opioids in any indication and at any dose. Gabapentin seems to present the same profile at least in observational studies.
Craving and addictive potential of esketamine as side effects?
Published in Expert Opinion on Drug Safety, 2022
Laura Orsolini, Virginio Salvi, Umberto Volpe
Overall, craving is described as a subjective experience frequently reported by those subjects who are dependent on addictive substances. Craving may manifest as a sense of subjective and irrefrenable desire toward the use of that substance. Craving may often intrude into the daily life of the patient, dominating his/her thoughts and provoking considerable distress and associated symptomatology, such as restlessness, anxiety, inner tension, sleep disorders, and so forth. Craving is also measured as an indirect predictor of subsequent risk for substance use relapse and represents a predictor of illness prognosis [37,54]. Thus, reducing the level of craving has been reported as resulting in better treatment outcomes [37,56]. Tolerance is a condition manifesting as a decrease in response toward a specific substance, which may manifest after a repeated use of a substance; while the sensitization is a sort of ‘reverse tolerance’ or an increase in response which the subject may manifest to a substance [24]. The development of tolerance and sensitization can be influenced by several factors, such as the dose, the interval between doses and specific environmental factors [24]. The development of tolerance to the therapeutic effect of a drug can determine a less effectiveness of that drug over time, while sensitization to a side effect can produce escalating problems with repeated use of that drug [24]. Tolerance to the desired effects of a substance of abuse (such as ketamine and esketamine) may lead to its increased use with the attempt to overcome the decreased effect. The development of tolerance and withdrawal syndrome, including craving, euphoria, and relaxation effects, as well as loss of control of drug-seeking behaviors have been hugely documented after chronic and recurrent ketamine use [25,31,34,36–38]. In fact, a compulsory and repetitive ketamine self-administration could potentially promote sensitization of chemical routes within the addiction window, which can be clinically expressed with the onset of craving symptomatology [24]. Tolerance can be pharmacologically explained by an extensive ketamine self-induction of its metabolism and by adaptions in dopaminergic and glutamatergic relays of various CNS pathways, such as the cortico-striato-thalamic and the cortico-limbic circuits [57–59].