Drug-Drug Interactions of MDMA

Alcohol The pharmacokinetic and pharmacodynamic interactions of single doses of ecstasy 100 mg and alcohol 0.8 g/kg have been investigated in nine healthy men (mean age 23 years) in a double-blind, double-dummy, randomized, placebo-controlled crossover design. Each underwent four 10-hour experimental sessions, including blood sampling, with 1 week between each. For the task used to test the recognition and recording of visual information, the conditions involving ethanol yielded significantly more errors and fewer responses than ecstasy alone or placebo alone. The combination of ecstasy with ethanol reversed the subjective effect of sedation caused by alcohol alone. In addition, the combination extended the sense of euphoria caused by ecstasy to 5.25 hours. The addition of ethanol caused plasma ecstasy concentrations to rise by 13%. These results show that the combination of ecstasy with alcohol potentiates the euphoria of ecstasy and reduces perceived sedation. However, psychomotor impairment of visual processing caused by alcohol is not reversed. This is a concern for road safety, as people who take both drugs would feel sober, but their driving would still be compromised, although the extent of driving impairment Read more […]

Drug-Drug Interactions of Methadone

Antiretroviral drugs Methadone is often used for opioid replacement therapy in intravenous drug abusers. The incidence of HIV infection is significantly higher in this population than in the general public, and interactions with drugs used for the treatment of AIDS are therefore important. Methadone is predominantly metabolized by CYP3A4. Antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (for example efavirenz, abacavir, and nevirapine) and/or a protease inhibitor (for example amprenavir) will induce the metabolism of methadone. This therapeutic combination is becoming increasingly common in HIV-positive substance misusers. Two studies have explicitly shown a significant reduction of methadone concentration by 28-87%. In the first study, 11 patients taking methadone maintenance therapy were given efavirenz and had a mean increase in methadone dosage requirement of 22%. In the second study, five methadone-maintained opioid-dependent individuals were given a combination of abacavir and amprenavir; the methadone concentration fell to 35% of the original concentration within 14 days. In a prospective study of 54 patients taking antiretroviral drugs who also took methadone and a further Read more […]

Drug-Drug Interactions of Amphetamines

Adrenergic neuron blocking drugs Amphetamines and other stimulatory anorectic agents, apart from fenfluramine, would be expected to impair the hypotensive effects of adrenergic neuron blocking drugs such as guanethidine. Not only do they release noradrenaline from stores in adrenergic neurons and block the reuptake of released noradrenaline into the neuron, but they also impair re-entry of the antihypertensive drugs. Alcohol Alcohol increases blood concentrations of amphetamines. Barbiturates Barbiturates can enhance amfetamine hyperactivity. Benzodiazepines Benzodiazepines can enhance amfetamine hyperactivity. Estradiol Preclinical studies (as well as anecdotal clinical reports) have shown that estrogens, through effects on the central nervous system, can influence behavioral responses to psychoactive drugs. In an unusual crossover study, the subjective and physiological effects of oral D-amfetamine 10 mg were assessed after pretreatment with estradiol. One group of healthy young women used estradiol patches (Estraderm TTS, total dose 0.8 mg), which raised plasma estradiol concentrations to about 750 pg/ml, and a control group used placebo patches. Most of the subjective and physiological effects of amfetamine Read more […]

Opioid-Related Disorders

Opioid abuse manifests in various ways in patients in medical settings. Psychiatrists are frequently consulted regarding opioid therapy for patients who are prescribed methadone, are thought or known to be dependent on prescription or illicit narcotics, engage in drug-seeking behavior, exhibit personality problems that interfere with medical care, or have overdosed. Suspicion is heightened by exaggerated pain complaints, by visits to multiple providers for multiple pain complaints requiring a narcotic prescription (e.g., migraine, back pain, dental pain, fibromyalgia, and endometriosis), and by claims to be “allergic” to every analgesic except for particular opioids (e.g., hydro-codone or oxycodone). Opioid-dependent patients often provoke angry reactions from staff, which can result in discharging a patient prematurely or underprescribing pain medications. Chronic pain patients who develop tolerance to opioids and experience opiate withdrawal on cessation of use are often misla-beled addicts (see “Pain”). Tolerance and withdrawal alone are not sufficient for the diagnosis of either substance abuse or dependence. For example, cancer patients with painful bone metastatic lesions may need high doses of narcotics and Read more […]