Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers

doi:10.1016/0091-3057(94)90338-7

Pharmacology Biochemistry and Behavior

Volume 48, Issue 3, July 1994, Pages 715-721

https://doi.org/10.1016/0091-3057(94)90338-7 Get rights and content

Abstract

The reasons why individuals use this combination are not entirely clear, however, it has been speculated that marihuana may potentiate cocaine's subjective effects. Five male recreational drug users provided informed consent and volunteered to participate in this study. Each subject participated on 3 different days, separated by at least 1 week. Subjects sat in an isolated chamber and were prepared with electrocardiographic (ECG) electrodes for heart rate monitoring and an IV catheter for blood withdrawal. After adapting to the experimental chamber, they smoked a marihuana cigarette containing either 0.004% (placebo), 1.24%, or 2.64% Δ⁹-tetrahydrocannabinol (THC). Thirty minutes later they received an intranasal dose of 0.9 mg/kg cocaine. On subsequent visits, the marihuana dose was varied on a random basis. Subjects continuously reported changes in their mood state via an instrumental joystick device and filled out visual analog scales. Marihuana-induced tachycardia was increased even more after cocaine. The duration of all marihuana- and cocaine-related positive subjective effects was unchanged when both drugs were given, but marihuana pretreatment significantly reduced the latency to cocaine effects, from 1.87 to 0.53 min, and decreased the duration of dysphoric or bad effects, from 2.1 to 0.5 min. Peak plasma cocaine levels were 122.8 ± 26.6 ng/ml after placebo marihuana, but pretreatment with the high-dose marihuana resulted in a significant increase in peak cocaine levels (233.8 ± 19.2 ng/ml) and the apparent bioavailability as determined by area under the curve (AUC) analysis. We conclude that marihuana-induced vasodilation of the nasal mucosa attenuates the vasoconstrictive effects of cocaine and thus increases its absorption.

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Polysubstance use is highly prevalent among persons who use cocaine; however, little is known about how alcohol and cannabis are used with cocaine. We identified temporal patterns of cocaine+alcohol and cocaine+cannabis polysubstance use to inform more translationally relevant preclinical models.
Participants who used cocaine plus alcohol and/or cannabis at least once in the past 30 days (n=148) were interviewed using the computerized Substance Abuse Module and the newer Polysubstance Use–Temporal Patterns Section. For each day in the past 30 days, participants reported whether they had used cocaine, alcohol, and cannabis; if any combinations of use were endorsed, participants described detailed hourly use of each substance on the most “typical day” for the combination. Sequence analysis and hierarchical clustering were applied to identify patterns of timing of drug intake on typical days of cocaine polysubstance use.
We identified five temporal patterns among the 180 sequences of reported cocaine polysubstance use: 1) limited cocaine/cocaine+alcohol use (53%); 2) extensive cannabis then cocaine+alcohol+cannabis use (22%); 3) limited alcohol/cannabis then cocaine+alcohol use (13%); 4) extensive cocaine+cannabis then cocaine+alcohol+cannabis use (4%); and 5) extensive cocaine then cocaine+alcohol use (8%). While drug intake patterns differed, prevalence of use disorders did not.
Patterns were characterized by cocaine, alcohol, and cannabis polysubstance use and by the timing, order, duration, and quantity of episode-level substance use. The identification of real-world patterns of cocaine polysubstance use represents an important step toward developing laboratory models that accurately reflect human behavior.
Smoked cannabis reduces peak cocaine plasma levels and subjective effects in a controlled drug administration study of polysubstance use in men
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Understanding the nature of cannabis-cocaine interactions will provide clinically relevant information that identifies abuse liability and health risks while laying the groundwork for developing treatment strategies. Initial laboratory studies indicate that acute cannabis exposure may enhance behavioral and physiological responses to insufflating or intravenous cocaine (Foltin and Fischman, 1989; Foltin et al., 1995; Foltin et al., 1987; Foltin et al., 1993; Lukas et al., 1994). However, these early studies did not consistently use a cannabis-only condition in the study design to assess potential additive effects of the drugs.
Despite the high prevalence of polysubstance use, outcomes and potential risks associated with common drug combinations are not well characterized. Many individuals who use cocaine also use cannabis, yet little is known about how interactions between the two drugs might contribute to continued co-use.
The aim of this double-blind, placebo-controlled study was to determine the physiological and subjective effects of smoked cannabis with smoked cocaine, to identify variables that may contribute to the continued use of this drug combination. Healthy, non-treatment seeking volunteers who reported smoking both cocaine and cannabis (N = 9, all males) completed a 13-day inpatient protocol. On session days, cannabis [0.0 or 5.6 % tetrahydrocannabinol (THC)] was administered 28 min prior to cocaine (0, 12, or 25 mg). Dependent measures included pharmacokinetic assessment of THC and cocaine and their respective metabolites, in addition to subjective and cardiovascular effects.
Active cannabis (5.6 % THC) increased plasma levels of THC and the metabolite 11-nor-9-carboxy-Δ9-THC (THCCOOH), as well as subjective ratings of cannabis effects and heart rate relative to inactive cannabis. Cocaine dose-dependently increased plasma cocaine and metabolites and subjective ratings of cocaine effects. Active cannabis pre-treatment decreased plasma levels of cocaine and metabolites. Furthermore, active cannabis attenuated cocaine-related reductions in ‘Hunger’ and ‘Calm.’
Cannabis pre-treatment altered the subjective experience of smoked cocaine and reduced peak plasma levels of cocaine. Future studies should explore additional doses of each drug and whether these changes also impact cocaine’s reinforcing effects.
Cannabis-drug interactions: Implications for medicinal cannabis use
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Medicinal cannabis (MC) products are typically derived from the plant Cannabis sativa. Hence, patients using MC are taking an entourage of constituents including major cannabinoids delta-9-tetrahydrocannabinol (△9THC), cannabidiol (CBD), and cannabinol as well as other cannabinoids and non-cannabinoid phytochemicals. In addition to △9THC and CBD, which are known to affect the drug-metabolizing P450 enzymes, many of these other constituents have been reported to have pharmacologic activity as well as activity on these and other drug-metabolizing enzyme systems. The study of drug-drug interactions with MC must include consideration of all of these constituents.
Unlike pharmaceuticals that undergo United States (US) Food and Drug Administration approval system, other than △9THC and CBD, the constituents of MC are not standardized from product to product or even within the same product over time. Therefore, it is possible that there are drug-drug interactions that change between refills and/or over time.
It is well established that MC use may result in pharmacokinetic and/or pharmacodynamic drug-drug interactions. However, there is much uncertainty for the clinician treating patients with MC products regarding potential for clinically significant interactions with other pharmaceutical agents used by those patients.
This chapter describes: (1) the effects of various constituents of MC on drug-metabolizing enzyme systems; (2) formulation and route of administration variables that can influence cannabinoid concentrations and ratio of drug to active metabolite, which may affect the likelihood of a drug–drug interaction; and (3) drug-drug interactions that have been reported clinically in peer-reviewed literature. This is a dynamic field that will likely undergo much change in the near future.
Effects of cocaine and/or heroin use on resting cardiovascular function
2021, International Journal of Cardiology: Cardiovascular Risk and Prevention
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Moreover, these drugs can modulate effects of cocaine and/or heroin. For example, by attenuating vasoconstrictive effect of cocaine, cannabis-induced vasodilation enhances absorption of cocaine and its toxic effects [37]. Such findings suggest clinicians should consider demographics, BMI, and polysubstance use when examining cardiovascular effects of individual drugs.
Regular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease, but confounded by other factors. We examined effects of chronic (years regular use) and recent (past-month) cocaine and heroin use, controlling for other factors, on resting cardiovascular function.
In a sample of 292 cocaine and/or heroin users, we assessed demographics, body mass index (BMI), substance use history, electrocardiogram, heart rate (HR) and blood pressure (BP). Three-block (1: demographics, BMI; 2: tobacco, alcohol, cannabis; 3: cocaine, heroin) regression analyses were conducted to predict cardiovascular measures.
Higher BMI predicted increased systolic and diastolic BP (as did older age), increased supine HR, and longer QRS duration, QTc interval, PR interval, and P-wave duration. Past-month cannabis-use days predicted higher systolic BP, lower supine HR, and greater likelihood of early repolarization and ST elevation; average daily cannabis use predicted shorter QTc interval. Average daily alcohol use predicted higher diastolic BP, higher supine HR and lower likelihood of sinus bradycardia (HR < 60 bpm). Past-month tobacco-use days predicted shorter QTc interval and lower lower likelihood of profound bradycardia (HR < 50 bpm). Past-month heroin-use days predicted lower seated HR, greater likelihood of sinus bradycardia and lower likelihood of left ventricular hypertrophy. More years of regular cocaine use and past-month cocaine-use days predicted longer QTc interval.
Cocaine and heroin use incrementally predicted modest variance in resting bradycardia and QTc interval. Clinicians should first consider demographics and recent use of tobacco, alcohol and cannabis before assuming cocaine and heroin affect these measures.
The importance of considering polysubstance use: lessons from cocaine research
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Polysubstance use (PSU) is prevalent among individuals with substance use disorders, but the vast majority of preclinical substance use research has focused on individual substances in isolation. Cocaine has been prevalent in the repertoire of persons who use more than one illicit substance.
We conducted a meta-analysis combining results from literature searches and secondary data analyses to estimate the prevalence of simultaneous and concurrent cocaine + alcohol and cocaine + cannabis use among cocaine users. We next summarized the small body of literature on behavioral, cognitive and neurobiological consequences of cocaine PSU across species, with a focus on alcohol and cannabis. Finally, we used systematic literature searches to assess the extent to which human and animal studies on the neurobiological consequences of cocaine include PSU subjects.
The estimated prevalence of simultaneous and concurrent alcohol use among human cocaine users was 74% and 77%, respectively. The estimated prevalence of simultaneous and concurrent cannabis use among cocaine users was 38% and 64%, respectively. Consumption of alcohol or cannabis with cocaine enhances subjective responses to cocaine, concomitant with changes in cocaine metabolism that increase blood cocaine levels, and, in the case of alcohol, produce the psychoactive metabolite cocaethylene. There is also consistent evidence for neurobiological effects of cocaine + alcohol combinations. However, animal PSU research with cocaine lags behind human research.
Based on the prevalence and known consequences of PSU, consideration of PSU in both human and animal research is vital for understanding patterns of substance use.
Relation of Cannabis Use and Atrial Fibrillation Among Patients Hospitalized for Heart Failure
2018, American Journal of Cardiology
Citation Excerpt :
Our study utilized the largest available inpatient data in the United States to examine this association and adjusted for all known risk factors of AF. In addition, cannabis users are most likely abusers of other recreational drugs such as opioid, amphetamine, psychostimulants, cocaine, sedatives, antidepressants, and hallucinogens known to have adverse effects on the cardiovascular system.39–41 It is possible that polysubstance use accounts for the incidences of AF seen in these case reports.
Left ventricular dysfunction triggers the activation of the sympathetic nervous system, providing inotropic support to the failing heart and concomitantly increasing the risk of atrial fibrillation (AF). The cardiovascular effects of cannabis have been characterized as biphasic on the autonomic nervous system with an increased sympathetic effect at low doses and an inhibitory sympathetic activity at higher doses. It is unknown if the autonomic effect of cannabis impacts the occurrence of AF in patients with heart failure (HF). We used data from the Healthcare Cost and Utilization Project–National Inpatient Sample for patients admitted with a diagnosis of HF in 2014. The outcome variable was the diagnosis of AF, with the main exposure being cannabis use. We identified a cannabis user group and a 1:1 propensity-matched non–cannabis user group, each having 3,548 patients. We then estimated the odds of AF diagnosis in cannabis users. An estimated 3,950,392 patients were admitted with a diagnosis of HF in the United States in 2014. Among these, there were 17,755 (0.45%) cannabis users. In the matched cohort, cannabis users were less likely to have AF (19.08% vs 21.39%; AOR 0.87 [0.77 to 0.98]). In conclusion, cannabis users have lower odds of AF when compared with nonusers, which was not explained by co-morbid conditions, age, insurance type, and socioeconomic status.

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Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers

Abstract

Life Sci.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

J. Chromatogr.

Toxicol. Appl. Pharmacol.

Patterns of nonopiate/polydrug abuse: Findings of a national collaborative research project

Effects of delta-9-tetrahydrocannabinol on drug distribution and metabolism: Antipyrine, pentobarbital, and ethanol

Clin. Pharmacol. Ther.

Polydrug abuse-status report on the federal effort

Multiple drug use of marihuana users

Dis. Nerv. Syst.

Enzymes in anesthesiology

Effects of marijuana, cocaine, and task performance on cardiovascular responsivity

Effects of the combination of cocaine and marijuana on the task elicited physiological response

Drug abuse by alcoholics: A review

Int. J. Addict.