hauptmann

These two articles I ran across back in the day really helped me understand not only how THC works but the correlation between dose and effect. I'm only going to post the portions that I really liked but I encourage everyone to read both of the articles in full, they are not very long. While I dont agree in full with the terminology used in these articles they are very interesting none the less.

Marijuana & the Human Brain

Marijuana & the Human Brain: The Tolerance Factor


THC: DOSE AND EFFECT

The effects of marijuana share certain properties with all the other psychoactive drugs - stimulants, sedatives, tranquilizers and hallucinogens. Scientists are just now figuring out how marijuana users manipulate dosage and tolerance to manage those effects.

Small doses of THC provide stimulation, followed by sedation. Large doses of THC produce a mild hallucinogenic effect, followed by sedation and/or sleep. The effects of mild "hypnogogic" states produced by THC are often undetected, contributing to mood variations from gregariousness to introspection.

The effects of marijuana can be sorted into four categories. First, there are modest physical effects, such as a slight change in heart rate or blood pressure and changes in body temperature. Tolerance develops to these effects with familiarity and/or regular use.

Tolerance next develops to the depressant effects of marijuana, particularly to its effects on motor coordination. However, tolerance to these effects depends on the quality of the marijuana consumed as well as the frequency of use. THC is one of several cannabinoids in marijuana. While it is the only cannabinoid to produce the psychoactive or stimulative effects, another cannabinoid, named cannabinol (CBN), produces only the depressant effects. CBN is generally present in low-potency marijuana, or very old marijuana in which the THC has decayed; it accounts for the generally undesirable effects of bad pot. While cannabinol gets someone "stoned," THC gets them "high."

After a while, tolerance develops to even the stimulative effects of marijuana. Experienced users learn that there is an outer limit to how high they can get. Paradoxically, this limit can only be exceeded by lower consumption.

Patients who require marijuana for medical purposes generally discover what dose provides steady maintenance of therapeutic benefits and tolerance to the side effects, both depressant and stimulative.


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HOW TO STAY HIGH: LESS IS MORE

The NIMH tolerance study confirms what most marijuana smokers have already discovered for themselves: The more often you smoke, the less high you get.

The dose of THC used in the study was 10 mg per kilogram of body weight, a dose frequently used in clinical research. What is the equivalent of 10 mg/kg of THC in terms of human consumption?

While most users are familiar with varying potencies of marijuana, many are only vaguely aware of differences in the efficiency of various ways to smoke it. Clinical studies indicate that only 10 to 20% of the available THC is transferred from a joint cigarette to the body. A pipe is better, allowing for 45% of the available THC to be consumed. A bong is a very efficient delivery system for marijuana; in ideal conditions the only THC lost is in the exhaled smoke.

The minimum dose of THC required to get a person high is 10 micrograms per kilogram of body weight. For a 165-pound person, this would be 750 micrograms of THC, about what is delivered by one bong hit.

The THC doses used on the NIMH rats were proportionately ten times greater than what a heavy human marijuana user would consume in a day. Assuming use of good-quality, 7.5% THC sinsemilla, it would take something like 670 bong hits or 100 joints to give a 165-pound person a 10 mg-per-kg dose of THC.

Obviously, the doses used are excessive. But the study indicates that the body itself imposes an unbeatable equilibrium on cannabis use, a ceiling to every high.

According to Herkenham's team: "The result [of the study] has implications for the consequences of chronic high levels of drug use in humans, suggesting diminishing effects with greater levels of consumption."

Tolerance and the quality of the marijuana both affect the balance between the two tiers of effects: the coordination problems, short-term memory loss and disorientation associated with the term "stoned" and the pleasurable sensations and cognitive stimulation associated with the word "high."

The distinction between the two states is nothing unique. Alcohol, nicotine and heroin can all produce nausea when first used; this symptom also disappears as tolerance to the drug develops. To conclude that marijuana users consume the drug to get "stoned" would be as accurate as asserting that alcohol drinkers drink in order to vomit.

One result of the NIMH study is that there is now a clinical basis for characterizing the differences between these two tiers of effects. In clinical terms, the effects of one-time (or occasional) exposure are referred to as the acute effects of marijuana. Repeated use or exposure is referred to as chronic use.

In addition to the now-disproved claims of dependence, opponents of marijuana-law reform always refer to the acute effects of the drug as proof of its dangers. Prohibitionists believe that tolerance is evidence that marijuana users have to increase their consumption to maintain the acute effects of the drug. No wonder they think marijuana is dangerous!

Marijuana-law reform advocates, more familiar with actual use patterns and effects, always consider the effects of chronic use as their baseline for describing the drug. "Chronic use" is just regular use, and there is nothing sinister about regular marijuana use.

Most marijuana users regulate their use to achieve specific effects. The main technique for regulating the effects of marijuana is manipulating tolerance. Some people who like to get "stoned" on pot, which (unlike the initial side effects of other drugs) can be enjoyable. These people smoke only occasionally.

People who like to get "high" tend to smoke more often, and maintain modest tolerance to the depressant effects. But this is not an indefinite continuum. Just as joggers encounter limits, regular users of marijuana eventually confront the wall of receptor down-regulation. Smoking more pot doesn't increase the effects of the drug; it diminishes them.

The ideal state is right between the two tiers of effects. One of the great ironies of prohibition is that most marijuana users are left to figure this out for themselves. Most do, and strive for the middle ground. Some just don't figure it out, and this explains two behaviors which are identified as marijuana abuse.

First is binge smoking, often but not exclusively exhibited by young or inexperienced users who mistakenly believe that they can compensate for tolerance with excessive consumption. The second behavior these new findings on tolerance explain is the stereotype of the stoned, confused hippie. According to this NIMH study, tolerance develops faster with high-potency cannabinoids. People who have irregular access to marijuana, and to low-quality marijuana at that, do not have the opportunity to develop sufficient tolerance to overcome the acute effects of the drug.

Another popular misconception this study contradicts is that higher-potency marijuana is more dangerous. In fact, the use of higher-potency marijuana allows for the rapid development of tolerance. Earlier research by Herkenham established why large doses of THC are not life-threatening. Marijuana's minimal effects on heart rate are still mysterious, but there are no cannabinoid receptors in the areas of the brain which control heart function and breathing. This research further establishes that the brain can safely handle large, potent doses of THC.

Like responsible alcohol drinkers, most marijuana users adjust the amount of marijuana they consume - they "titrate" it - according to its potency. In the course of a single day, for example, the equilibrium is between the amount consumed and the potency of the herb. Tolerance achieves the same equilibrium; over time the body compensates for prolonged exposure to THC by reducing the number of receptors available for binding. The body itself titrates the THC dose.

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