Analgesic and antiinflammitory effects of C.Sativa

[Guest Wilderbud]

This research paper confirms my suspisions that CBD is the better part of marijuana for pain relief. I leave my stash in the light usually and I get better pain relief after a day or two in the light.

 

Ive noticed that the pot turns to crap after a week of this so I think Ill just have some next to the bowl for the next day from now on instead of leaving it up to my subconscous to provide a good stone [it gets forgetful after a few sessions I suppose - heh].

 

Oh yeah, I call CDB-dominant weed sleep-weed for a reason - after a few days of stoned-sleep it feels like Ive got a new back so it [leaving the weed in the light for a day or two] would be good to try on weekends if you havent tried it and are a medicinal smoker.

[syk613]

Hi wilderbud, I had a look at your post and it is some very interesting info. 9-THC is spontaneously converted to cannabinol. ref Rang, Dale, Ritter, Pharmacology (more info on this ref in the med effects thread I started.)

but the rest comes from herehttp://www.nih.gov/news/medmarijuana/Medic...na.htm#CLINICAL

 

I hope something is helpful, goodluck mate, and there is lots more info at the above link for med uses etc , and if you have any questions do not hesitate to ask.

Cannabinoids of Importance

 

 

 

THC, the main psychoactive cannabinoid in marijuana, is an optically active resinous substance. THC is not soluble in water but is extremely lipid soluble (Agurell et al. 1984, 1986; Mechoulam 1973). Varying proportions of other cannabinoids, mainly cannabidiol (CBD) and cannabinol (CBN), are also present in marijuana, sometimes in quantities that might modify the pharmacology of THC or cause effects of their own. CBD is not psychoactive but has significant anticonvulsant, sedative, and other pharmacologic activity likely to interact with THC (Adams and Martin 1996; Agurell et al. 1984, 1986; Hollister 1986a).

 

 

 

The concentration of THC and other cannabinoids in marijuana varies greatly depending on growing conditions, plant genetics, and processing after harvest (Adams and Martin 1996; Agurell et al. 1984; Graham 1976; Mechoulam 1973). In the usual mixture of leaves and stems distributed as marijuana, concentration of THC ranges from 0.3 percent to 4 percent by weight. However, specially grown and selected marijuana can contain 15 percent or more THC. Thus, a marijuana cigarette weighing 1 gram (g) might contain as little as 3 milligrams (mg) of THC or as much as 150 mg or more.

 

Analgesia

 

 

 

No clinical trials involving smoked marijuana have been performed in patients with naturally occurring pain. Two adequate and well-controlled studies in cancer pain compared graded doses of oral 9-THC to placebo, and one of these included graded doses of codeine as a control. Although there was evidence of analgesic efficacy, the studies indicate there is a narrow therapeutic margin between the doses that produce useful analgesia and those producing unacceptable adverse CNS effects

 

 

 

Analgesia

 

 

 

1. What research has been done and what is known about the possible medical uses of marijuana?

 

 

 

A number of studies have been conducted on the antinociceptive or analgesic effect of tetrahydrocannabinol (THC) or marijuana in both animals and human subjects; the results have been conflicting. Of interest is the recent identification of cannabinoid receptors as well as an endogenous ligand, anandamide. There is some evidence that they are part of a natural pain control system distinct from the endogenous opioid system. Recognizing that some studies have demonstrated an antinociceptive (analgesic) effect of THC and related compounds in rodents, it may be useful to identify what specific kinds of pain may be relieved by marijuana or THC.

 

 

 

Animal studies on the analgesic effect of marijuana have produced inconsistent results. Whereas one study shows that delta-9-tetrahydrocannibinol (9-THC) is equipotent to morphine in rats (tailflick test), and more potent than morphine in mice (hotplate test), other studies showed that 9-THC was less potent than morphine in both mice and rats. Cannabinoids have been shown to be possibly analgesic in animal models of neuropathic pain.

 

 

 

There have been a few studies of marijuana/9-THC employing different models of experimentally induced pain in volunteer subjects, and these studies have also yielded conflicting results. Raft and colleagues (1977) found that, in oral surgery patients, premedication with intravenous 9-THC was less effective than diazepam or placebo in reducing two kinds of experimentally induced pain. Another study showed that smoked marijuana increased pain tolerance, while others showed either no effect or a lowering of pain threshold after oral or intravenous dosing with 9-THC or smoking marijuana. The current "FDA Guideline for the Clinical Evaluation of Analgesic Drugs" (FDA 1992) notes that "Evidence is still inadequate to establish that any experimental pain model will consistently and accurately predict the clinical efficacy of new analgesics, . . . [and] they cannot substitute for controlled trials in patients with pathologic pain [naturally occurring pain caused by disease or tissue injury] in producing substantial evidence of analgesia . . ." This is also the overwhelming consensus of investigators who conduct controlled clinical trials of analgesic efficacy. Therefore, the above studies contribute little information about the analgesic efficacy of marijuana/9-THC in patients with pain.

 

 

 

There appear to be no controlled analgesic studies of smoked marijuana in patients with naturally occurring pain. However, Noyes and his colleagues conducted two studies of oral 9-THC in inpatients with cancer pain. Both of these studies used the same standard single-dose analgesic study methodology and met the criteria for well-controlled clinical trials of analgesic efficacy, but with small sample sizes. Both were randomized, double-blind, crossover comparisons employing a full-time nurse-observer, who collected hourly subjective ratings of pain intensity and pain relief. Observed and reported side effects were recorded, as were the responses to an 11-item subjective effects questionnaire.

 

 

 

The first study in 10 cancer patients compared a placebo and 5, 10, 15, and 20 mg doses of 9-THC over a 6-hour observation period (Noyes et al. 1975a). The slope of the dose-response curve for pain relief was significant, as was a pairwise comparison of pain relief after the two lower doses combined versus the two higher doses combined. There was also a clear dose-response relationship for sedation, mental clouding, and other central nervous system (CNS) related side effects. Because of sedation, the 20-mg dose was judged to be "of limited value for most patients."

 

 

 

The second study in 36 cancer patients compared placebo, 10, and 20 mg of 9-THC and 60 and 120 mg of codeine over a 7-hour observation period (Noyes et al. 1975b). Codeine 120 mg and 9-THC 20 mg were similar to each other and significantly superior to placebo for the sum of the pain intensity differences and total pain relief, while other pairwise contrasts were not significant. Relative potency analysis was not performed.

 

 

 

The time-effect curves for both doses of codeine and for 9-THC, 10 mg, peaked at the third hour. As in the first study, the 20 mg dose of 9-THC peaked at the fifth hour, which probably reflects the delayed absorption of oral THC. "Patients receiving 20 mg of THC were heavily sedated and even at 10 mg reported considerable drowsiness. Other dose limiting side effects included dizziness, ataxia and blurred vision" (Noyes et al. 1975b). Mental clouding, thinking impairment, disconnected thought, disorientation, slurred speech, and impaired memory were much more prominent after both doses of 9-THC than after codeine administration, and patients expressed particular concern over their "loss of control" over thought and action. Five patients experienced very unpleasant psychic effects after 9-THC; three patients said they felt as if they were dying, one patient experienced depressed mood, and one patient suffered paranoid ideation. In two patients, the adverse mood effects persisted 3 or 4 days.

 

 

 

These studies indicate that 9-THC has some analgesic activity in humans. They also indicate that there is, at best, a very narrow therapeutic window between doses that produce useful analgesia and those that produce unacceptable adverse CNS effects.

 

 

 

2. What are the major unanswered scientific questions?

 

 

 

Since oral 9-THC has some analgesic activity, it is highly likely that smoked marijuana has some analgesic activity in some kinds of clinical pain. Because 9-THC from smoked marijuana is absorbed directly into the pulmonary circulation, this route of administration results in a 9-THC blood level curve much more like that produced by an intravenous injection than that after oral administration. It is therefore likely that smoked marijuana potentially allows a more precise titration to effect than oral administration of 9-THC with its delayed, poor, and erratic bioavailability. Theoretically, smoked marijuana or inhaled THC potentially has some of the characteristics of a patient-controlled analgesia (PCA) pump. It is therefore possible that some pain patients could use smoked marijuana to titrate themselves into the therapeutic window of adequate pain relief while avoiding unacceptable adverse effects. Although the above scenario is pharmacologically reasonable, only properly designed controlled clinical analgesic studies can determine if it actually works and is practically useful. For example, it is also possible that the minimum blood level of 9-THC that produces useful analgesia also usually produces a level of sedation, mental clouding, and thinking impairment that is unacceptable to most patients.

 

 

 

There are currently available a great variety of both opioid and nonsteroidal anti-inflammatory drug (NSAID) analgesics in various dosage formulations suitable for many routes of administration. Adroit use of these can manage most acute pain and even chronic cancer pain satisfactorily. If marijuana is to be a useful analgesic, healthcare providers need to know how it compares in efficacy and safety to at least a few of the standard analgesics that would be used in managing a particular kind of pain.

 

 

 

3. What are the diseases or conditions for which marijuana might have potential as a treatment and which merit further study?

 

 

 

Neuropathic pain represents a treatment problem for which currently available analgesics are, at best, marginally effective. Since 9-THC is not acting by the same mechanism as either opioids or NSAIDs, it may be useful in this inadequately treated type of pain. Evaluation of cannabinoids in the management of neuropathic pain, including HIV-associated neuropathy, should be undertaken. A few animal studies support this idea. Another potentially useful role for marijuana/9-THC might be as an adjuvant when added to a regimen of standard analgesics.

 

References

 

 

 

FDA Guideline for the Clinical Evaluation of Analgesic Drugs. DHHS Pub. No. 93-3093. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Food and Drug Administration, 1992.

 

Noyes, R., Jr.; Brunk, S.F.; Baram, D.A.; and Canter, A. Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol 15(2-3):139-143, February-March, 1975a.

 

Noyes, R., Jr.; Brunk, S.F.; Avery, D.A.H.; and Canter, A.C. The analgesic properties of delta-9-tetrahydrocannabinol. Clin Pharmacol Ther 18(1):84-89, July, 1975b.

 

Raft, D.; Gregg, J.; Ghia, J.; and Harris, L. Effects of intravenous tetrahydrocannabinol on experimental and surgical pain. Clin Pharmacol Ther 21(1):26-33, 1977.