Revival: Cannabis Physiopathology Epidemiology Detection (1992)

Gabriel G. Nahas

• Publisher: CRC Press
• Year: 2017
• ISBN:
  9781351367813
• Edition: 1
• Topic: Medicine
• Subtopic: Epidemiology

Cannabis Physiopathology and Detection features an outstanding collection of contributions from leading researchers around the world. Papers were presented at the Second International Colloquium on Illicit Drugs, held at the French National Academy of Medicine in April 1992. The book reviews the latest clinical reports describing the effects of cannabis on the brain (imaging techniques, memory and psychomotor performance, cannabis, and schizophrenia), effects on reproduction (male and female), and carcinogenicity. Aspects of detection covered in the volume include methods, results of different testing groups, and legal issues associated with testing and detection.Cannabis Physiopathology and Detection will be an important addition to the reference collections of marijuana researchers, pathologists, government agencies, medical school libraries, and drug testers.

Section I
Physiopathology

1. Toxicology

General Toxicity of Cannabis

Gabriel Nahas, M.D., Ph.D.
New York University, Medical Center, New York and Laboratoire de Toxicologic Cellulaire, Hôpital F. Widal, Paris.

Abstract

The physiopathological effects of marihuana smoke and of its constituent cannabinoids were reported first from in vitro and in vivo experimental studies. Marihuana smoke is mutagenic in the Ames test and in tissue culture and cannabinoids inhibit biosynthesis of macromolecules. Exposure of animals to THC or marihuana produces symptoms of neurobehavioral toxicity, disruptive effects on all phases of gonadal or reproductive function and is fetotoxic. Smoke inhalation produces symptoms of airway obstruction and squamous metaplasia-Ten years after completion of these experimental studies, clinical manifestation of marihuana physiopathology are now reported. These include: long term impairment of memory storage in adolescents; prolonged impairment of psychomotor performance, resulting in lethal train and car accidents; residual impairment of plane piloting; a six fold increase in incidence of schizophrenia; cancer of mouth, jaw, tongue and lung in 19 to 30 year old; non-lymphoblastic leukemia in children from marihuana smoking mother and fetotoxicity.

Key Words

Marihuana, mutagenicity, fetotoxicity, neurobehavioral toxicity, impairment memory, performance, schizophrenia, cancer, leukemia.

Introduction

The recreational smoking of products derived from Cannabis sativa, mainly its resin (hashish) or the chopped flowering tops of the plant (marihuana) has become widespreaded in western industrialized countries since 1960. Because of its lack of acute life threatening effects, cannabis has been called a "soft drug.", no less damaging than coffee or tobacco (1). This designation might have to be revised, in view of its prolonged impairing effects on memory and learning and its residual neuropsychopharmacological properties and its effects on lung, on immunity system and reproductive function, which have only been recently reported (2) and which confirm earlier experimental observations (3).

General Properties of Cannabis

Products extracted from the Cannabis sativa plant for purposes of smoking originate from the drug-type of the plant, which grows in warm climes of Africa, Americas, South East, Asia, Australia and New Zealand. The flowering tops of cannabis contain an intoxicating material, delta-9-tetrahydrocannabinol (THC), which may vary from 1 to 6% of the total weight: 1 to 3% in grass or marihuana, up to 8% in hashish and exceeding 50% in hash oil. In contrast, the fiber-type of cannabis, which grows in cool climates and is used for the manufacture of rope and twine, contains very little THC. In addition to THC, over 60 other cannabinoids have been identified in cannabis, mainly cannabiniol (CBD) and cannabinol (CBN) which are not psychoactive but are biologically active. Cannabis also contains 8 different classes of compounds (4), numbering 421 and which are for the most part xenobiotics, such as (Table I): Alkaloid derivatives of spermidine, sterols, terpenes and flavanoid glucosides.

Under the influence of heat, cannabinoids rapidly decarboxylate. At the temperature of pyrolysis (200-400°C), aromatization of the cannabinoids occurs. Some 150 polycyclic aromatic hydrocarbons have been identified in marihuana smoke and the proportions of the higher molecular weight compounds, particularly the carcinogen benzo[a]pyrene, are greater in marihuana than in tobacco smoke, suggesting higher toxicity. The most likely sources of these hydrocarbons are the cannabinoids. Other constituents of marihuana smoke include phenols, phytosterols, acids and terpenes. In other respects the smoke of tobacco and marihuana are similar, as can be seen from Table 1. Toxic substances such as carbon monoxide, hydrogen cyanide, and nitrosamines are present in equivalent concentrations in both smokes, and the "tar" yield is also similar.

THC and other cannabinoids are very fat-soluble and have a half-life of 8 days in fat. It therefore takes one month to completely eliminate a single dose of THC, which is stored in liver, lung, spleen and mostly in neutral fat. Consumption of cannabis at less than one-week intervals will result hi storage of THC in the body. THC is a polar compound and is slowly metabolized into more water-soluble, non-psychoactive metabolites, 80 of which have been identified to date. The bioavailability of inhaled THC is 20 %, and when ingested, it is 6%. Less than 1% of the bioavailable THC reaches the brain, a fact which illustrate the psychoactive potency of this drug (6). Excretion of metabolites is via the liver and intestine (80%), with entero-hepatic

TABLE I
COMPARATIVE ANALYSIS OF MAINSTREAM SMOKE FROM MARIHUANA AND TOBACCO REFERENCE CIGARETTE.
(Average weight: 1.110 mg; Length: 85 mm)

Measurements	Marihuana Cigarette	Tobacco Cigarette
Gas phase
Carbon monoxide, vol.%	3.99	4.58
Carbon dioxide, vol.%	8.27	9.38
Ammonia, μg	228	199
HCN, μg	532	498
Cyanogen (CN)2, gg	19	20
Isoprene, μg	83	310
Acetaldehyde, μg	1,200	980
Acetone, μg	443	578
Acrolein, μg	92	85
Acetonitrile, μg	132	123
Benzene, μg	76	67
Toluene, μg	112	108
Vinyl chloride, ng*	5.4	12.4
Dimethylnitrosamine, ng*	75	84
Methylethylnitrosamine, ng*	27	30
Particulate phase
Total particulate matter, dry, mg	22.7	39
Phenol, μg	76.8	138.5
O-Cresol, μg	17.9	24
m- and p- Cresol, μg	54.4	65
Dimethylphenol, μg	6.8	14.4
Catechol, μg	188	328
Cannabidiol, μg	190	-
Delta-9-tetrahydrocannabinol, μg	820	-
Cannabinol, μg	400	-
Nicotine, μg	-	2,850
N-Nitrosonornicotine, ng*	-	390
Naphthalene, μg	3	1.2
1-Methylnaphthalene, μg	6.1	3.65
2-Methylnaphthalene, μg	3.6	1.4
Benz(a)anthracene, ng*	75	43
Benzo(a)pyrene, ng*	31	21.1

* indicates known carcinogens.

From Marihuana and Health, National Academy of Sciences, Institute of Medicine Report, Washington, D.C., 1982.

recirculation which delays their elimination; urinary excretion does not exceed 20%. In addition, THC and its metabolites cross the placental barrier and are transferred to maternal milk.

The acute and chronic physicopathological effects of marihuana smoking may be related to three of its following properties.

- The property of THC, its psychoactive ingredient to attach, in nanomolar concentration to specific receptors in hippocampus, cerebellum and frontal lobes.

- The property of all psychoactive and nonpsychoactive cannabinoids and their metabolites to inhibit in micromolar concentration macromolecular synthesis.

- The properties of toxic xenobiotics contained in the gas and particulate phase of cannabis smoke.

EFFECTS OF THC ON THE BRAIN:
an impairment of information processing

The THC receptor and its distribution in the brain

THC interacts in nanomelecular concentration with stereospecific receptors first described in 1990 by Herkenham et al (7). They used a tritiated synthetic cannabinoid CP 54940, much more active than THC and presenting marked enantiomer selectivity. They were able to localize a specific receptor on brain slices sampled from rat, rhesus monkey and man. Herkenham reported that the density of the THC receptors in every animal species studied, followed the same distribution. It was especially marked in the limbic area, (globus pallidus and substantia nigra), hippocampus, cerebellum and frontal lobes.

The THC receptor was cloned by Matsuda (8) et al and THC cannabinoid was the only molecule which attached to the G protein coupled receptor, and exhibited adenylyl cyclase inhibition in transf...

Table of contents

• Cover
• Half Title
• Title
• Copyright
• List of Contributors
• Foreword
• Preface
• Introduction
• Greetings from the Academy
• Contents
• I. PHYSIOPATHOLOGY
• II. EPIDEMIOLOGY
• III. DETECTION, IDENTIFICATION AND TESTING
• General Conclusions
• Appendix
• Index