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Director's Report to the National Advisory Council on Drug Abuse
September, 1995

Research Findings

Clinical and Services Research

Physiological and Subjective Responses to Food Cues as a Function of Smoking Abstinence and Dietary Restraint

Tobacco smokers gain weight after quitting smoking with women usually gaining more weight than men. This weight gain after quitting smoking appears to be from increased eating, especially of sweet-tasting between-meal snacks. The investigators examined the influence of smoking abstinence on physiological (salivary habituation) and subjective (cigarette desire, hunger, taste liking, emotional arousal) responses to food cues in women smokers, 10 each in high or low dietary restraint groups, respectively. Dietary restraint is associated with chronic concerns about weight and dieting to attempt to maintain an unreasonably low body weight and is measured by the Revised Restraint Scale of Herman and Polivy. The subjects were divided into two groups: those who scored >15 (high restraint) and low restrainers who scored <15 on the scale. The salivary responses to taste increased significantly more in high vs. low restraint women smokers during the first trial of taste, especially on the smoking day. However, the salivary habituation to strawberry yogurt was significantly disrupted by smoking abstinence in high restraint women. High restraint women also reported increasing desire for cigarettes and emotional arousal across food taste trials on both days, while the low restraint women reported no changes over trials. Results indicate that brief smoking abstinence attenuates salivary habituation to taste in high restraint women, suggesting a marker for processes responsible for increased food intake after quitting smoking. Repeated exposure to food stimuli may also increase emotional distress in high restraint women smokers, enhancing desire to smoke (Perkins KA, Mitchell SL, Epstein LH, Physiol Behav 58(3):000-000, 1995).

Individual Variability in Responses to Nicotine:

Individual variability in acute responses to nicotine is generally attributed to stable characteristics of tobacco users such as genetic/constitutional factors (e.g., gender) and chronic environmental experience (behavioral factors). Perkins et al. show that the situational factors such as acute stress or physical activity may also play an important role in variability to nicotine effects. The situational influences may determine why smokers are more likely to smoke under certain conditions, such as high stress. Females may be more responsive than males to non-nicotine stimuli associated with smoking (e.g., sight and taste of smoke). The effects of many psychoactive drugs (including nicotine) on behavior may be strongly determined by the situational context surrounding drug intake (e.g., accompanying environmental and social stimuli, temporal factors), and not simply the pharmacology of the drug. The pre-drug subjective state, ongoing level of physical activity vs. rest, and concurrent drug intake, all are situational factors that may result in individual variability in nicotine's subjective, behavioral, and physiological responses (Perkins, Behavior Genetics, 25(2): 119-132, 1995).

Cannabis Psychotic Disorder: Does it Exist?

Although "cannabis psychotic disorder"with delusions or with hallucinations is recognized in DSM-IV, relatively little information is available on the entity. Pope and his colleagues reviewed 395 eligible charts of the 9,432 admissions at two psychiatric centers between 4/91 and 10/92, and 10/89 and 11/92, respectively, seeking cases of cannabis-induced disorders. There were no convincing cases of a cannabis-induced psychotic syndrome. The authors also reviewed published studies on the subject. There were 10 series of 10 or more cases, all describing primarily cannabis-induced psychotic syndromes. None of the ten studies was performed in the US; only two were published in the last 10 years and neither supported the existence of a distinct cannabis-induced psychosis. Further, most studies were retrospective and uncontrolled. The overall evidence from both reviews was inadequate to be certain that cannabis alone can produce a psychotic syndrome in previously asymptomatic individuals. The authors suggest that further research is needed to validate the diagnosis of cannabis psychosis (Gruber AJ and Pope, HG, American Journal on Addictions, 1(1):72-83, 1994).

Attributes of Heavy vs. Occasional Marijuana Smokers in a College Population:

Forty-five long-term heavy marijuana smokers were compared with 44 occasional smoker students who were drawn from two Boston colleges. The heavy smokers smoked marijuana daily for at least two years (an average of approx. 27d in the last month) and the "occasional" smokers never smoked more than ten times in a month at any time in their lives (average 2.7d in the last month). The drug use was assessed by urine toxicology screen. Heavy smokers reported higher rates of use of other substances, especially hallucinogens and cocaine, and described greater subjective impairment of memory and motivation than occasional smokers. However, on a wide range of demographic, family-background, and mental health measures, the heavy smokers proved almost indistinguishable from occasional smokers. The authors conclude that even the heaviest college marijuana smokers exhibit few demographic or psychiatric features which distinguish them from students who smoke only occasionally (Kouri E, Pope HG, Yurgelun-Todd D, and Gruber S, Biological Psychiatry, in press).

Substance Use Reduction in the Context of Outpatient Psychiatric Treatment: A Collaborative, Motivational, Harm Reduction Approach:

Carey's conceptual model incorporates four themes familiar to addiction treatment researchers and demonstrates how these can work within ongoing mental health treatment. The themes are: treatment intensity, stages of change, motivational interventions, and harm reduction. The five steps of the model include:
  1. establishing a working alliance,
  2. evaluating the cost-benefit ratio of continued substance use,
  3. individualizing goals for change,
  4. building an environment and lifestyle supportive of abstinence, and
  5. anticipating and coping with crises.

This model integrates clinical realities of mental health treatment with empirically-grounded strategies applicable to substance abuse problems (Carey, Community Mental Health Journal, in press).

Gender Differences in Cerebral Perfusion in Cocaine Abuse: Technitium-99m-HMPAO SPECT Study of Drug-Abusing Women:

Mendelson and his colleagues measured cerebral perfusion of 13 cocaine-dependent men (average age of 32.4+6.7 years) and 13 women (average age of 34.6+4.6 years), and an equal number of controls. The investigators found that cocainedependent women had much less abnormal findings of cerebral perfusion (both in terms of number of defects/patient and the proportion of patients affected) than cocaine-dependent men and were indistinguishable from normal women. These gender differences could not be explained by age, race, body mass index, alcohol use, amount of cocaine use, amount of heroin use, the route of drug administration, or any other structural abnormality. The underlying mechanism of these gender differences remains to be established.

The concurrent use of heroin and cocaine was associated with more perfusion abnormalities in both sexes, that has been reported also in animals (Levin JM, Holman LB, Mendelson JH, Teoh SK, Garda B, Johnson KA, Springer S, Journal of Nuclear Medicine, 35(12):1902-1909, 1994).

Increased Mu-opioid Receptors in Cocaine Abuse Demonstrated by PET: Association with Craving:

Frost and his colleagues examined mu-opioid receptor binding in ten cocaine dependent men and seven non-addicted controls using positron emission tomography and 11C-carfentanil. Mu-opioid binding was increased (range 25-50%) in several brain regions (caudate, thalamus, and neocortical regions) of the cocaine addicts studied 1-4 days after their last use of cocaine. Craving was significantly correlated with mu-opioid binding in amygdala, anterior cingulate gyrus, frontal and temporal cortex and negatively correlated with the urinary levels of the cocaine metabolite benzoylecgonine prior to scanning. The upregulatory changes observed persisted after 4 weeks of monitored cocaine abstinence in the majority of subjects. These findings demonstrate for the first time the involvement of the endogenous opioid system in cocaine dependence and cocaine craving in living human subjects (Zubieta JK, Gorelick D, Stauffer R, Dannals RF, Ravert HT, and Frost J, presented at the 42nd Annual Meeting of the Society of Nuclear Medicine, June-12-15, 1995, Minneapolis, MN).

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