Background—Marijuana use in the age group prone to coronary artery disease is higher than it was in the past. Smoking marijuana is known to have hemodynamic consequences, including a dose-dependent...

Triggering Myocardial Infarction by Marijuana

To compare the pulmonary hazards of smoking marijuana and tobacco, we quantified the relative burden to the lung of insoluble particulates (tar) and carbon monoxide from the smoke of similar quantities of marijuana and tobacco. The 15 subjects, all men, had smoked both marijuana and tobacco habitually for at least five years. We measured each subject's blood carboxyhemoglobin level before and after smoking and the amount of tar inhaled and deposited in the respiratory tract from the smoke of single filter-tipped tobacco cigarettes (900 to 1200 mg) and marijuana cigarettes (741 to 985 mg) containing 0.004 percent or 1.24 percent delta 9-tetrahydrocanabinol. As compared with smoking tobacco, smoking marijuana was associated with a nearly fivefold greater increment in the blood carboxyhemoglobin level, an approximately threefold increase in the amount of tar inhaled, and retention in the respiratory tract of one third more inhaled tar (P less than 0.001). Significant differences were also noted in the dynamics of smoking marijuana and tobacco, among them an approximately two-thirds larger puff volume, a one-third greater depth of inhalation, and a fourfold longer breath-holding time with marijuana than with tobacco (P less than 0.01). Smoking dynamics and the delivery of tar during marijuana smoking were only slightly influenced by the percentage of tetrahydrocanabinol. We conclude that smoking marijuana, regardless of tetrahydrocannabinol content, results in a substantially greater respiratory burden of carbon monoxide and tar than smoking a similar quantity of tobacco.

Pulmonary hazards of smoking marijuana as compared with tobacco

Lumbar cerebrospinal fluid homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5HIAA), and probenecid were measured in groups of patients suffering from schizophrenia or affective disorder following administration of probenecid (100 mg/kg over 18 hours) to block acid monoamine metabolite egress from cerebrospinal fluid (CSF). The CSF HVA value was lower in the total schizophrenic group compared with that of the affective disorder group and in a poor prognosis group of schizophrenics compared with that in a good prognosis group. These differences could not be accounted for by differences in CSF probenecid. Comparable net increases in HVA were produced by antipsychotic drug administration in subgroups from the two groups of schizophrenics. If clinical schizophrenia is characterized by increased central dopaminergic transmission, this increased transmission is not associated with increased central HVA formation, as determined by the measurement of lumbar CSF HVA following probenecid.

Central Dopamine Turnover in Schizophrenic Syndromes

Designer drugs have been problematic over the years. Products such as K2 and Spice, which contain synthetic cannabinoids, are marketed as incense and are widely available on the Internet and at various specialty shops. The effects are reported as cannabis-like after smoking them. In addition, use of these synthetic cannabinoids will not appear on a routine urine toxicology screen. Recently, K2 became a popular alternative to marijuana among youths. Health implications of these designer drugs are not completely understood. Little has been reported about the harmful effects of K2. We report here the first (to our knowledge) cases of myocardial infarction (MI) after smoking K2. Three patients presented separately to the emergency department complaining of chest pain within days after the use of K2. Acute MI was diagnosed in each case on the basis of electrocardiogram changes and elevated troponin levels. Coronary angiography was performed, and the results were normal for the first 2 patients. The incidence of ST-elevation MI is low among teenagers, and association with drug use should be suspected. Public education and awareness need to be heightened about the possible health implications of K2.

Myocardial Infarction Associated With Use of the Synthetic Cannabinoid K2

Probenecid inhibits the removal of 5-HIAA and HVA (the major metabolites of serotonin and dopamine) from the cerebrospinal fluid. The accumulation of these metabolites following high doses of probenecid was studied in patients with affective illness in order to assess central amine function. The metabolite accumulation was increased by administering the appropriate precursors (which increase amine synthesis) and was decreased by administering specific synthesis inhibitors. Compared with controls, the depressed patients had low HVA accumulation, while addicts on methadone had low 5-HIAA accumulation. Within the group of depressed patients, HVA accumulation was higher in bipolar than in unipolar patients.

Cerebrospinal fluid amine metabolites in affective illness: the probenecid technique.

Rapid elevation of biogenic amine metabolites in human CSF following probenecid.

The effects of a pharmacologic dose of delta‐9‐tetrahydrocannabinol (Δ‐9‐THC) on the human circulatory system were investigated. Their relation to plasma drug levels, urinary catecholamine excretion, and psychic effects was observed. Δ‐9‐THC (0.3 mg. per kilogram) was administered orally to 8 male volunteers. Four subjects also received tracer amounts of C14‐Δ‐9‐THC. Recumbent and upright heart rate, recumbent mean arterial blood pressure, forearm blood flow, and calculated forearm conductance all increased significantly following drug administration. Significant shortening of ventricular pre‐ejection period and attenuation or abolition of reflex venoconstriction in response to a deep breath were also seen. Mean arterial pressure decreased transiently with head‐up tilt and was associated with presyncope in 7 subjects, although cardioacceleratory response and forearm arteriolar constriction remained intact. Plasma levels of C14Δ‐9‐THC and its metabolites were maximal at 3 hours. Gastrointestinal absorption was 95 per cent complete. Urinary excretion of free epinephrine was significantly higher during the 6 hour period following Δ‐9‐THC administration than during a similar control period. Free norepinephrine excretion was unchanged. Several of the cardiovascular effects seen appear to be consistent with increased sympathoadrenal activity. This suggests the possibility that augmented epinephrine secretion is in part responsible for these Circulatory changes.

Norman R. Tamarkin

Papers

Rapid elevation of biogenic amine metabolites in human CSF following probenecid.

Cardiovascular effects of delta-9-tetrahydrocannabinol in man