West Virginia University School of Medicine Department of Behavioral Medicine and Psychiatry

Ehab Abdallah M.D.

Marijuana
Medical Friend or Foe

Classifying Marijuana
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Marijuana produces some excitatory effects but it is not generally regarded as a stimulant. Marijuana produces sedative effects, but a person faces no risk of slipping into a coma or dying. Marijuana produces mild analgesic effects, but it is not related pharmacologically to opiates like drugs. Marijuana produces hallucinations at high doses, but its structure does not resemble LSD or any other drug formally categorized as hallucinogen.

So marijuana is clearly a hybrid drug in a league of its own.

Basic Terminology
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Marijuana is

frequently a synonym for cannabis but technically the two terms are separate.

Cannabis is the

botanical term for the hemp plant cannabis sativa.

Brief History
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Cannabis sativa have been commercially valuable for thousands of years in the manufacture of rope, shoes, sailcloth, and containers of all kinds. Pots made of hemp fiber discovered at archeological sites in China date the origins of cannabis as far back as the Stone Age. Cannabis sativa is arguably the oldest cultivated plant not used for food.

Spaniards brought cannabis to the New World in 1545.

English settlers brought it to Jamestown, Virginia in 1611 as a major commercial crop along with tobacco. In the eighteenth-century George Washington grew cannabis on his farm. Entries in his diary indicated that he maintained a keen interest in cultivating better strains of cannabis, but there is no reason to believe he was interested in anything more than a better quality of rope.

Marijuana – The Plant

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Marijuana is obtained from serrated leaves from the cannabis plant. The key psychoactive factor is contained in a sticky substance, or resin, that accumulates on these leaves. Depending on the growing conditions, cannabis will produce either a greater amount of resin or greater amount of fibers.

Marijuana – The Plant

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In hot, dry climates such as North Africa the fiber content is weak but so much resin is produced that the plant looks as if it is covered with dew. In cooler more humid climates such as North America less resin is produced but the fiber is stronger and more durable.

Definitions
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Cannabinoids: Any of the several dozen active substances in marijuana and other cannabis products. Delta-9-tetrahydrocannainol (THC): The active psychoactive ingredient in marijuana and hashish. Marijuana: The most commonly available psychoactive drug originated from the cannabis plant. The THC concentration ranges from approximately 1 to 4 percent.

Definitions
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Sinsemilla: A form of marijuana obtained from the un-pollinated or seedless portion of the cannabis plant, it has a higher THC concentration than regular marijuana, as high as 6 percent. Hashish: A drug containing the resin of cannabis flowers, the THC concentration ranges from approximately 8 to 14 percent.

Definitions
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Hashish Oil: A drug produced by boiling hashish, leaving the potent psychoactive residue, the THC concentration ranges from approximately 15 to 60 percent. Hashish oil crystals: Solid form of hashish oil. Bhang: A liquid form of marijuana, popular in India.

The History of Marijuana and Hashish

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The first direct reference to a cannabis product as a psychoactive agent dates from 2737 B.C. in the writings of the Chinese emperor Shen Nung. The focus was on its powers as a medication for rheumatism, gout, malaria, and strangely enough absentmindedness. In India the use was clearly recreational as the most popular form is liquid made from cannabis leaves called Bhang.

History
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The Muslim world also grew to appreciate the psychoactive potential of cannabis, encouraged by the fact that ,in contrast to its stern prohibition of alcohol consumption, The Koran did not specifically ban its use. In Iran, because of the hot dry climate and high resin content of the cannabis, hashish was born and its popularity spread quickly during the twelfth century from the east to North Africa in the West.

Hashish in the Nineteenth Century

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Before the nineteenth century hashish was not known in Europe, Pope Innocent VIII in 1484 condemned witchcraft and the use of hemp in the Black Mass . By 1800 marijuana was widely used for two reasons: 1) French soldiers who had served in Napoleon‟s campaigns in Egypt brought hashish back with them to their homes in France. 2) The wave of romanticism that swept over Europe, including an increased interest in exotic stories of the East, such as Arabian Nights and The Tales of Marco Polo which contained references to hashish.

Hashish in the Nineteenth Century

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In Paris during 1840‟s a small group of prominent French artists, writers and intellectuals formed the Club des Hachichins (Club of Hashish-Eaters), members included Victor Hugo. They gather “to take of literature, art and love” while consuming large quantities of hashish. The mixture consisted of a concentrated hemp paste, mixed with butter, sweeteners, and flavoring such as vanilla and cinnamon.

Marijuana and Hashish in the Twentieth Century

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By 1890, cotton had replaced hemp as a major cash crop in southern states although cannabis plant continued to grow wild along road sides and in the fields. It was not until the 1920‟s that marijuana began to be a noticeable phenomenon. Some authors had related the appearance of marijuana as a recreational drug to social changes brought on by prohibition when it was difficult to obtain good quality liquor at affordable prices. At first its recreational use was restricted to Jazz musicians and people in show business.

Marijuana and Hashish in the Twentieth Century

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Famous mainstream clarinetist and band leader Benny Goodman had his popular hit “Sweet Marihuana Brown”. Marijuana by that time was tolerated by authorities because it was not illegal. Marijuana was not considered as a social threat. In late the 1920‟s and the early 1930‟s there was a large migration of Mexicans to the United States, they entered the country through towns along the Mexican border and along the Gulf Coast.

Marijuana and Hashish in the Twentieth Century

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In Mexican communities marijuana was, in the words of one historian “a casual adjunct to life … a relaxant, a remedy for headaches, a mild euphoric cheaply obtained for two cigarettes for the dollar. Rumors about the violent behavioral consequences of marijuana smoking among Mexicans began to spread. The idea was unchallenged by objective data. Considering the hysteria against marijuana smoking and cannabis use in general Congress passed the Marijuana tax act of 1937.

Marijuana and Hashish in the Twentieth Century

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The marijuana regulation was accomplished indirectly as the act did not ban marijuana; it merely required everyone connected with marijuana, from growers to buyers to pay a tax. It was a simple procedure that, in effect, made it virtually impossible to comply with the law. In absence of compliance, a person was in violation of the act and therefore subject to arrest. During the 1940‟s and 1950‟s the theory that marijuana was connected to violence slowly faded away, only to be replaced by a new notion, the gateway theory. According to the gateway theory marijuana is dangerous because its abuse will lead to the abuse of heroin, cocaine, or other illicit drugs.

Marijuana and Hashish in the Twentieth Century

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Penalties for involvement with marijuana increased, in certain states the penalties were harsh. Judges had the option of sentencing a marijuana seller or user to life imprisonment. In Georgia, a second offence of selling marijuana to a minor could be punishable by death.
In 1969, the U.S. Supreme Court ruled the 1937 Marijuana Tax Act to be unconstitutional. The argument was made that requiring a person to pay tax in order to possess an illegal substance is a form of selfincrimination, which would be a specific violation of the fifth amendment to the constitution.

Reefer – A common name for a marijuana cigarette.

Joint – a marijuana cigarette.

Psychiatric Symptoms in Marijuana Users

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Effects of moderate intoxication (Zinberg et al) attitude and expectations or mental “set” and environmental combine with pharmacological effects to produce subjective experience of intoxication.
Euphoria – well-being and peacefulness are universally described in experimental studies in drug naïve and drug experienced volunteers. During cannabis intoxication an awareness of alteration in thought processes is frequently reported. Subjects may describe their thoughts as being fragmented (Ames, 1958) or more efficient than usual (Chopra & Smith, 1974).

Some cannabis users claim that after taking the drug they can recall distant memories to which they would not ordinarily have access to. (Tart, 1970). However experimental studies on the effect of THC on memory did not show any measurable effects on long term memory retrieval. Suspiciousness and paranoia are common experiences. Subjects also reported that time seems to pass more slowly. Marijuana smokers reported increase awareness of their surroundings as well as sharpened sense of sight and sounds.

Adverse Reactions
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Anxiety provoking with mild intoxication. Panic attacks – acute anxiety reactions to Marijuana may include restlessness, depersonalization, sense of loss of control, fear of panic and paranoia.

Cannabis induced psychotic reaction – Acute toxic confusion

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Toxic psychosis can follow ingestion of cannabis. Acute toxic psychosis is more common to occur with higher doses of Delta-9-THC. Typically symptoms are apprehension suspiciousness, confusion, memory impairment, depersonalization, derealization, and hallucination.

Psychiatric Symptoms in Cannabis Users: Table 1

Case reports of psychosis associated with cannabis use
COMMENTS Mental confusion and hallucinations in a Brazilian Indian who had smoked 2g cannabis. First time users. Description of symptoms is scanty. Had extreme paranoid reactions. No mention of outcome. Full report was of 6 cases – the other three experienced acute anxiety or depersonalization only. First-time users. All had impaired cognitive function. Ten had paranoid symptoms. Well (1970) comments that these may be true cases of toxic psychosis in view of the soldiers exceptional circumstances. Authors commented on the absence of previous psychosis of family history of psychosis. Schizophrenia-like acute psychosis in long-term users of beverage containing cannabis products („bhang‟). No pre-existing psychosis or abuse of other drugs. Marked confusion noted. Reported also included seven cases of „subacute‟ and „chronic‟ psychosis. Subject had a history of other drug abuse including „magic mushrooms‟. Three schizophreniform psychoses, two manic. Various clinical pictures – those with schizophreniform features had family histories of psychosis. None had abused alcohol or other drugs. One patient had features suggesting an acute toxic psychosis. YEAR 1955 1968 1969 1969 COUNTRY Brazil USA India Vietnam
(US soldiers) NUMBER OF CASES

1 3 3 12

1971 1973 1982 1983 1984 1984

USA India Sweden UK Anguilla UK

8 4 4 1 5 9

1986

UK

Psychiatric Symptoms in Cannabis Users: Table 2

Clinical studies of psychosis associated with cannabis use

YEAR 1972

COUNTRY USA

NUMBER OF SUBJECTS (type) 100 (Cannabis Users) 36,000 (US soldiers) 200 (Patients) 88 (In-patients)

DESIGN
Comparative

COMMENTS Psychiatric problems precede cannabis use.

1972

Germany

Descriptive

Confounded by use of other drugs and alcohol. Symptoms included disorientation and confusion. Symptoms included disorientation, amnesia and confusion. 37.5% of patients diagnosed as having a „schizophreniform‟ reaction had a history of cannabis use, while the figure was lower for all other diagnostic groups. Cannabis-using psychotics had a shorter course and more hypomanic symptoms than non-using psychotics.

1974

India

Descriptive

1976

Jamaica

Descriptive

1982

S. Africa

20 (In-patients)

Retrospective Case-control

Acute psychotic reaction in clear consciousness

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An acute psychotic reaction may follow cannabis use, clinical picture is characterized by rapid onset and mixture of affective and schizophrenic like symptoms.

Mood Disturbances
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Self-limiting, dysphoric reactions are well recognized consequences of cannabis use. Serious mood disturbances can occur with prolonged marijuana use, however this has not been supported by controlled studies. The increased risk of suicide found in one large study needs further consideration. Clinical reports have suggested that cannabis use may precipitate relapse in patients with preexisting depressive disorder.

Relationship to Schizophrenia
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Some authors found causative role for the drug use in the aetiology of chronic functional psychosis on the basis that drug using schizophrenic patients had better premorbid personalities and earlier age of onset than the non-users. Andreasson et al 1987 reported the result of prospective study of 45,570 Swedish patients over 15 year follow-up period the relative risk for developing schizophrenia was 2.4 for cannabis users compared to non-users and 6.0 for heavy users.

Marijuana appears to enhance or magnify positive symptoms of schizophrenia in established cases. Some patients use marijuana to counteract the side effects of neuroleptics, or to counteract the sense of loss or emptiness a schizophrenic may feel when his/her delusions or hallucinations are suppressed by medication. Peralta & Cuesta 1992 published a Spanish study of 95 schizophrenic patients, 23 were marijuana users, and found no difference in positive symptoms, but a significantly higher rate of negative symptoms among non-users.

The Residual Cognitive Effects of Heavy Marijuana Use in College Students Harrison G. Pope Jr. MD et al JAMA 1996
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Design – Single-blind comparison of regular users vs infrequent users of marijuana. Participants – Two samples of college undergraduates: 65 heavy users, and 64 light users. Intervention – Neuropsychological tests were administered to all subjects , all subjects were abstinent from marijuana and other drugs for a minimum of 19 hours before testing.

Results – Heavy users displayed significantly greater impairment than light users on attentional/executive functions . Conclusions – Heavy marijuana use is associated with residual neuropsychological effects even after a day of supervised abstinence from the drug.

Cognitive Functioning of Long-term Heavy Cannabis Users Seeking Treatment

Solowij, PhD et al JAMA 2002

Objective – To examine the effects of duration of cannabis use on specific areas of cognitive functioning . Design, Setting, and Participants Multisite retrospective cross-sectional neuropsychological study conducted in the US between 1997 and 2000 among 102 near-daily cannabis users (51 long-term users and 51 shorter-term users) compared with 33 nonuser controls.

Results – Long-term cannabis users performed significantly less well than shorter-term users and controls on tests of memory and attention. Long-term users showed impaired learning , retention , and retrieval compared with controls.

Conclusions – These results confirm that longterm heavy cannabis users show impairments in memory and attention that endure beyond the period of intoxication and worsen with increasing years of regular cannabis use.

Amotivational Syndrome
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1986 William McGlothin, a psychologist, and Louis West, a psychiatrist, proposed that chronic marijuana smoking among young people was responsible for amotivational syndrome. Regular marijuana use may contribute to the development of more passive, inward turning personality characteristics, for numerous middle class students, the subtly progressive change from conforming, achievement-oriented behavior to a state of relaxed and careless drifting has followed their use of significant amount of Marijuana. Such individuals exhibit greater introversion, become totally involved with the present at the expense of their future goals and demonstrate a strong tendency toward regressive, childlike magical thinking.

Cardiovascular Effect
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“circulation 2001”

Smoking marijuana increase heart rate, supine hypertension and postural hypotension. Mittleman MD. reported triggering myocardial infarction with marijuana. Interviewed 3,882 patients with acute M.I an average of 4 days after infarction onset. Of the 3,882 patients 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of M.I. symptoms.

Compared with non-users marijuana users were more likely to be:

Men  Current cigarette smokers  Obese
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Marijuana smokers were less likely to:

Have history of angina  Hypertension
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Risk of M.I. was elevated 4.8 times over baseline in the 60 minutes after marijuana use, the elevated risk rapidly decreases thereafter. Conclusions – smoking marijuana is a rare trigger of acute M.I.

Myocardial Infarction Following the Combined Recreational Use of Viagra and Marijuana
“clinical cardiology 2002”

Viagra is widely prescribed treatment for male erectile dysfunction. Viagra is metabolized by the cytochrome P450 3A4 hepatic microsemal isoenzyme. Marijuana is an inhibitor of the cytochrome P450 3A4 isoenzyme.

Case report about myocardial infarction following combined use of viagra and marijuana.
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Male age 41 years old Non-smoker No history of D.M. or HTN No family history of premature coronary artery disease No past history of impotence Admit smoking marijuana the previous evening and taking recreationally one tablet of viagra 12 hours before onset of chest pain. Myocardial infarction was confirmed by EKG and cardiac enzymes.

Effects on sexual functioning and reproduction

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Men
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Reduces level of testosterone Reduces sperm count Increases percentage of abnormally formed sperm.

Women
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Reduction in level of lutenizing hormone (LH), a hormone necessary for fertilized egg to be implemented in the uterus.

Medical Uses for Marijuana

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Glaucoma
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Smoking marijuana reduces I.O.P. in normal human subjects. THC eye drops reduce glaucoma symptoms.

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Asthma
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Initial bronchodiltion, followed by bronchoconstriction.

Nausea
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Cancer treatment. AIDS patient.

The End