H. Rowland Pearsall

A pilot study of dextromethorphan in naloxone-precipitated opiate withdrawal

Dextromethorphan and its metabolite dextrophan antagonize N-methyl-D-aspartate (NMDA)-mediated activity in pre-clinical studies. We examined dextromethorphans effects on naloxone-precipitated opiate withdrawal in opiate-dependent subjects stabilized on 25 mg of methadone. Subjects received challenges on three different days with 0.4 mg of intramuscular naloxone. Pretreatment 1 h before naloxone was with dextromethorphan in a double-blind, balanced, randomized design with either placebo, dextromethorphan 60 mg, or dextromethorphan 120 mg for six subjects; and placebo, dextromethorphan 120 mg, or dextromethorphan 240 mg for five subjects. There was considerable inter-individual variability in the response to dextromethorphan, but no net attenuation by dextromethorphan on any withdrawal measure assessed. Two of three subjects detoxified from methadone with dextromethorphan 60 mg orally every 4 h demonstrated considerable withdrawal.

The effect of lamotrigine on naloxone-precipitated opiate withdrawal.

We hypothesized that lamotrigine, a putative glutamate release antagonist, would attenuate glutamate-mediated signs of opiate withdrawal. Seven heroin-dependent subjects were hospitalized, stabilized on oral levorphanol 6 mg three times daily, and thrice underwent withdrawal precipitated by naloxone 0.4 mg intravenously. Lamotrigine (placebo, 250 mg, and 500 mg) was randomly given as a pretreatment 6 h before naloxone. Lamotrigine did not significantly attenuate any measure of opiate withdrawal. Lamotrigine was well-tolerated in subjects, although one did develop an allergic rash.

The Effect of Gamma-Hydroxybutyric Acid on Naloxone-Precipitated Opiate Withdrawal

Because gamma-hydroxybutyric acid (GHB), a GABA metabolite, attenuated spontaneous opiate withdrawal in a prior study, we studied GHBs effect on naloxone-precipitated opiate withdrawal. Eight opiate-dependent inpatients were stabilized on the opioid levorphanol, 18 mg daily. After an initial acclimatization challenge, subjects underwent three double-blind challenges on consecutive days. Pretreatment in a balanced randomization was with either placebo, GHB, 15 mg/kg, or GHB, 30 mg/kg, followed an hour later by intravenous naloxone, 0.4 mg/70 kg. GHB produced no significant attenuation of multiple withdrawal measures except for hot-cold feelings. GHB pretreatment slightly accelerated respiration prior to naloxone. Differences with prior studies may be due to (1) timing of GHB administration (giving postwithdrawal in prior studies), (2) direct reversal of GHBs anti-withdrawal effects by naloxone, or (3) differences between naloxone-precipitated and spontaneous opiate withdrawal.

Dose dependent effects of yohimbine on methadone maintained patients.

Twelve methadone-maintained patients were randomized into a controlled crossover study with active and placebo yohimbine 20 mg once a day (n = 4), 5mg three times a day (n = 4) or 10 mg three times a day (n = 4) for seven days to evaluate the effect of yohimbine on naloxone precipitated opiate withdrawal. The yohimbine dose of 10 mg TID was well tolerated and was associated with an average decrease of 30% in precipitated withdrawal symptoms.

Interactions of cocaine with nimodipine: a brief report.

This double blind, placebo controlled study of acute calcium channel antagonist use during cocaine administration in five patients found that 60 mg of nimodipine treatment attenuated the systolic, but not diastolic, blood pressure effects of cocaine. In three subjects, a 90 mg dose of nimodipine showed a greater attenuation than that of 60 mg. Subjective effects of cocaine were not altered by either dose of nimodipine.

The impact of the Yale faculty development program: Clinical alcohol and drug research and education (cadre) on medical student teaching about substance abuse 1

Increasing emphasis on the need for medical student education about substance abuse has led to the development of a variety of training efforts through faculty development. The Yale University School of Medicine Faculty Development Program or CADRE (Clinical Alcohol and Drug Research and Education) was instituted in 1992 for the purpose of enhancing substance abuse teaching in the Yale medical student curriculum. CADRE faculty were identify in internal medicine, pediatrics, and psychiatry. Prior to the program, there was limited formal teaching about substance abuse in the Yale curriculum and no coordinated effort across disciplines. The enhancement of teaching activities occurred primarily within four required “core”; clinical clerkships for third‐and fourth‐year medical students. Student evaluations of this new teaching activity were positive. The CADRE program was successful at developing a multidisciplinary core faculty group with expertise in substance abuse teaching and resulted in the development o...