Chronic marijuana use is associated with increased cerebrovascular resistance through changes mediated, in part, in blood vessels or in the brain parenchyma. These findings might provide a partial explanation for the cognitive deficits observed in a similar group of marijuana users.

Rationale Although the subjective effects of caffeine abstinence, acute and chronic administration, and tolerance are well described, the corresponding neurophysiological effects are not. Objectives Caffeine withdrawal, acute caffeine effects, caffeine tolerance, and net beneficial effects of chronic caffeine administration were investigated using cerebral blood flow velocity, quantitative EEG and subjective effects. Methods Sixteen regular caffeine users participated in this double-blind, within-subject study during which they received acute caffeine and placebo challenges: 1) while maintained on 400 mg caffeine daily for ≥14 days and 2) while maintained on placebo for ≥14 days. Blood flow velocity was determined for the middle (MCA) and anterior (ACA) cerebral arteries using pulsed transcranial Doppler sonography. EEG was recorded from 16 scalp sites. Subjective effects were assessed with questionnaires. Results Acute caffeine abstinence (evaluated 24 hours after placebo substitution) increased mean, systolic and diastolic velocity in the MCA and ACA and decreased pulsatility index in the MCA. Acute caffeine abstinence increased EEG theta and decreased beta 2 power. Acute caffeine abstinence also increased measures of Tired, Fatigue, Sluggish and Weary and decreased ratings of Energetic, Friendly, Lively and Vigor. Acute caffeine effects were demonstrated across a wide range of measures, including cerebral blood flow, EEG and subjective effects. Tolerance and “complete” tolerance were observed on subjective but not physiological measures. Chronic caffeine effects were demonstrated only on the measure of EEG beta 2 power. Conclusion Acute caffeine abstinence and administration produced changes in cerebral blood flow velocity, EEG, and subjective effects. Tolerance to subjective but not physiological measures was demonstrated. There was almost no evidence for net effects of chronic caffeine administration on these measures. Overall, these findings provide the most rigorous demonstration to date of physiological effects of caffeine withdrawal.

Objective-Marijuana abuse is associated with neurological changes including increases in frontal EEG alpha during abstinence. Research is needed to assess to what extent these EEG patterns are indicative of cerebral perfusion deficits.Methods-We recorded the resting eyes closed EEG of 75 abstinent marijuana users and 33 control subjects. Fifty-six marijuana users used marijuana for less than eight years and 19 used for eight years or more. The EEG evaluation occurred within 72 hours of admission to an inpatient unit. Fiftynine marijuana users remained abstinent for a month and were tested twice. Supplemental psychological and physiological data were also collected.Results-Log alpha2 and beta2 power at posterior sites were significantly lower for the marijuana abusers that used eight years or more than the other marijuana abusers and the control subjects. These EEG changes continued for the month of abstinence. The marijuana users who used marijuana for more than eight years, also, had lower heart rates and thyroid function (T4) compared to the other marijuana users and the control subjects.Conclusions-Chronic marijuana use was also associated with reduced EEG power in alpha and beta bands at posterior sites. These reductions in EEG power appear to be related to cerebral perfusion deficits and/or thyroid function in marijuana abusers.Significance-Our results suggest EEG, cerebral blood flow velocity, cardiovascular and thyroid function alterations in marijuana abuser with an extended period of use. These alterations reflect under arousal in these systems.

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