CANNABIS and DEPENDENCE ON MEDS
Oct 2005

We are all dependant on something: Man is a creature of habits. We can arrange our priorities, minimize the harms of both our habits and our meds with a little thought. We've all heard the endless television medical commercials. A soothing voice begins to extol the virtues of a pharmaceutical drug, then to list the adverse effects, then, as if they hadn't just told you that these chemicals can fry your brain or deteriorate your body, the calming voice urges you to get your doctor to prescribe this medicine to make your life perfect.

I once called a pharmaceutical company to ask why they didn't encourage the marketing of medical marijuana? Was it because as a plant it can't be patented? Or perhaps because they could make more money off the chemical forms? Or because if doctor's were able to prescribe marijuana, patients could grow their own and pharmaceutical profits would drop by an estimated 20%. The rep became enraged at the last suggestion. "Marijuana would never cause a drop in our sales," he blustered. "Well, I know I'd be using it" I responded and that was the end of that.

As I may have told you, for years I was caregiver to several very sick people who used marijuana to raise their quality of life. One lady who has Ehlors Danlos Syndrome keeps a tackle box, where she has carefully seperated and labled the seeds from her medicinal plants as for "deep bone pain" or "sleep" or "to eat". The patients have studied the effects of this plant deeper than anyone conducting studies for the federal reps because for them their health and well-being is urgent. So much for the scientific community.
Kay Lee

Medical Cannabis Reduces Patients' Reliance On Other Medications Study Says

Sydney, Australia
October 6, 2005

More than half of Australians who use cannabis medicinally use it to treat symptoms of chronic pain and depression, and more than 60 percent report that it has led to a decrease in their use of standard pharmaceuticals, according to survey data published in the October issue of the Harm Reduction Journal.

One hundred and twenty-eight Australians with a long-term history of medical cannabis use participated in the survey, performed by the University of South Wales' National Drug and Alcohol Research Center. "[R]egular medical cannabis use was frequently reported for multiple medical conditions including chronic pain (57 percent), depression (56 percent), arthritis (35 percent), persistent nausea (27 percent) and weight loss (26 percent)," authors found. "Cannabis was perceived to provide 'great relief' overall (86 percent), and substantial relief of specific symptoms such as pain, nausea and insomnia. It was also typically perceived as superior to other medications in terms of undesirable effects, and the extent of relief provided."

Researchers further noted: "Almost two-thirds (62 percent) of respondents claimed they decreased or discontinued their use of other medicines when they started using cannabis medicinally. ... For some people this was a substantial change, representing a shift away from chronic, high-dose medication use."

Participants in the survey ranged from 24 to 88 years old, with more than half reporting having used cannabis medically for at least six years. Ten percent of respondents reported that they used cannabis on the recommendation of their physician.

Overall, respondents considered cannabis inhalation to be the most "helpful" route of administration for symptom relief, though many expressed concerns regarding the potential health effects of smoking.

"Consistent with users elsewhere, ... Australian medical cannabis users ... claim moderate to substantial benefits from [the drug's] use in the management of their medical condition ... [and] show strong interest in clinical cannabis research, including the investigation of alternative delivery methods," authors concluded.

For more information, please contact Paul Armentano, NORML Senior Policy Analyst, at (202) 483-5500. Full text of the study, "Survey of Australians using cannabis for medical purposes," is available online at: http://www.harmreductionjournal.com/

Source: NORML Foundation (DC)
Published: October 6, 2005
Copyright: 2005 NORML
Contact: norml@norml.org
Website: http://www.norml.org/

Health Aspects of Cannabis Dr. Leo Hollister
Tolerance and Dependence http://www.druglibrary.org/Schaffer/hemp/medical/hollisterhealth.htm

Tolerance to cannabis has long been suspected to occur during its continued use. Narrative accounts indicate that chronic users of the drug either show very little effect from moderate doses or require very large doses to produce characteristic intoxication. A pioneer study of subchronic administration of cannabis and synhexyl, a synthetic cannabinoid, suggests at best some degree of tolerance to the euphoriant actions (180). Yet it has only been in the past few years that tolerance to cannabis has been clearly documented experimentally.

The demonstration of tolerance in man was delayed by ethical restrictions on the amount of exposure permissible to human subjects. For instance, in an early study subjects were exposed only to a test dose of 20 mg of THC p.o. and then given the same doses or placebos repeated at bedtime for 4 more days, followed by the same THC dose as a challenge on the fifth day. Using such small doses and relatively infrequent intervals, it was impossible to show tolerance to the psychic effects of the drug, although the tolerance to the tachycardia and dizziness produced by the drug were evident (85).

Other early studies likewise suggested tolerance without definite proof. Tolerance to both tachycardia and "high" was reported following 21 days of consecutive smoking of only one cigarette a day by experienced smokers. It was possible that these subjects may have already been tolerant to the drug (46). Another study, in which subjects smoked a cannabis cigarette containing 14 mg THC for 22 days, revealed a progressive decline in the increase of pulse rate following smoking, an increase in alpha rhythm on the electroencephalogram, and more decrement in the performance of short­term memory and reaction time tasks (49).

A number of other early studies provided less evidence of tolerance. Little evidence of tolerance to clinical effects of cannabis was found from daily smoking of marijuana cigarettes over a period of 10 to 28 days (51, 142). Free choice of marijuana cigarette for 21 days also provided little evidence to support the concept of tolerance in man (165). Meanwhile, substantial evidence had accumulated that tolerance could be shown in various animal species, especially with high doses of THC given for prolonged periods.

Definite evidence of tolerance to the effects of THC in man was adduced only when it became permissible to use comparably large doses over longer periods of time. Subjects in one 30­day study were given high doses (70 to 210 mg/day) of THC p.o. around the clock. Tachycardia actually became bradycardia, and a progressive loss of "high" was noted (49). Similar tolerance to cannabis smoking was observed in a 64­day study in which at least one cigarette daily had to be smoked with smoking as desired later in the same day. Additionally, in this study tolerance developed to the respiratory depressant effect of THC (13).

The pattern that has emerged in man, therefore, is that tolerance is not a problem when the doses are small, or infrequent, or where the pattern of use of the drug is not

prolonged. Tolerance only becomes a major factor with high, sustained, and prolonged use of the drug. It is interesting that no study in man or animals ever revealed any evidence for "reverse tolerance" or sensitization, such as had been reported in an early, rather naive clinical study of marijuana (176).

1. Cross­tolerance. THC has effects which in man somewhat resemble those of hallucinogens and strongly resemble those of alcohol, while in animals it slightly resembles morphine. No cross­tolerance to mescaline or lysergide (LSD) could be shown in rats (151). Rats tolerant to the effects of THC were also tolerant to ethyl alcohol, but when the situation was reversed, less tolerance to THC was seen in the alcohol­tolerant animals (127). Perhaps this difference in sequential tolerance is why THC has never become established as a treatment for alcohol withdrawal, despite some early clinical trials that suggested a favorable effect. Cross­tolerance between THC and morphine has been shown in rats using customary tests of analgesia (95).

2. Physical dependence. Evidence from both animals and man indicates that physical dependence can be induced by abuse of THC. All monkeys given automatic injection doses of THC of 0.1 to 0.4 mg/kg showed abstinence signs when withdrawn. when monkeys were allowed to self­administer the drug for 3 to 8 weeks, the majority had an abstinence syndrome when the drug was abruptly discontinued. the syndrome appeared approximately 12 h after the last administration and lasted about 5 days. it was characterized by irritability, aggressivity, tremors, yawning, photophobia, piloerection, and penile erections (95).

In man, a somewhat similar, though mild, withdrawal reaction was uncovered after abrupt cessation of doses of 30 mg of THC given every 4 p.o. for 10 to 20 days. Subjects became irritable, had sleep disturbances, and had decreased appetite. Nausea, vomiting, and occasionally diarrhea were encountered. Sweating, salivation, and tremors were autonomic signs of abstinence (49). Relatively few reports of spontaneous withdrawal reactions from suddenly stopping cannabis use have appeared, despite the extraordinary amount of the drug consumed, Five young persons experienced restlessness, abdominal cramps, nausea, sweating, increased pulse rate, and muscle aches when their supplies of cannabis were cut off. Symptoms persisted for 1 to 3 days (15). The rarity of reports of these reactions may reflect the fact that they are mild, and seldom is a user completely cut off from additional drug.

Cannabis would have been an exceptional centrally acting drug if tolerance/dependence were not one of its properties. The fact that tolerance was not strongly recognized as an effect of chronic use was due to the narrative nature of previous accounts of tolerance in man and the lack of systematic animal experimentation. Tolerance has now been proven for most of the actions of THC. It develops at varying rates for different actions, but it is rapidly reversible. Large doses of THC are required over long time periods for tolerance to develop. As most social use of the drug does not meet those requirements, neither tolerance nor dependence has been a major issue in its social use.

Possible Accumulation of Drug

The major if not sole active component of cannabis, THC, is highly lipid soluble. As the human body has a high lipid content, which includes not only body fat, but also brain and most cell membranes, lipid­soluble drugs tend to leave the blood rapidly to be distributed to fatty tissues. It is characteristic of such drugs that the action of a single dose is terminated not by the elimination of the drug through metabolic processes, but by redistribution to sites in the body where it cannot act. The prime example of such a drug is pentothal sodium, which rapidly produces anesthesia when given i.v. but which has a very short span of action. the drug still remains in the body, but in places where it cannot act. A similar situation applies to the widely used sedative drug, diazepam.

An early study of the pharmacokinetics of THC examined its tissue distribution following a single injection of radiolabeled material, the concentration of THC in fat was 10 times greater than for any other tissue examined and persisted in this tissue for 2 weeks. Thus, there is good evidence that THC and its metabolites might accumulate not only in fat, but also in brain (107).

Obviously, similar studies could not be done in man. One can measure in man the extraction of cannabis metabolites following single or repeated doses, to get some idea of their persistence. Following both single and repeated doses (at least single doses for several days), metabolites of cannabis of cannabis can be found in urine for varying periods, up to several days following the last dose (94). All of these metabolites are ones that are known to have no mental effects, except for a minuscule amount of unchanged THC which is excreted during the first 4 h following a dose, while the drug is having definite clinical effects. The excretion of these metabolites is not accompanied by any evidence of cannabis­like effects.

We may conjecture that THC rapidly leaves the blood to be sequestered in fatty tissues. It is either gradually metabolized in these tissues to inactive metabolites which are then excreted in the urine, or it may be gradually released from these tissues in small amounts to be metabolized by the liver before attaining effective plasma concentrations. In either case, there is no evidence of a continuing drug effect from this accumulation of drug in the body.

In short, the apprehension about accumulation of THC from repeated use is based on evidence indicating only the accumulation of drug that is either in inactive form to begin with or which is rendered inactive before reaching the circulation in any pharmacologically active amount. We do not know the full toxicity of many of the possible metabolites which might accumulate, but generally toxicity studies of cannabis and its constituents lead to the inescapable conclusion that it is one of the safest drugs ever studied this way.

EMAIL  Kay Lee