sweep

dave, as I put it, check it out if you dare, knock yourself out. The main reason I posted my message was so that others who are going through similar experiences might benefit from my advice. Recently, on holiday, after my return from amsterdam to france, I fed my uncle three different kinds of hashish. At some point he was afraid of losing control. he had his head in his hands and he was doing the classic staring at tiles on the floor. I reassured him by offering similar words to the post above. 'you're becoming introverted. you'll start to think and thats when you can convince yourself that the world is going crazy and that you're going to go mad. instead, do something. go outside walk about and when you're in touch with the world, the paranoia will disappear.

It really does work- after being scared shitless on countless occasions over the years I feel qualified to offer my judgement on feelings of paranoia and fear, which is a common part of heavy marijuana use. If others can benefit from my posts then all is well. I am not a sick man anymore.

on a final note, the other night I sat and imagined what the universe would sound like, if I could hear it. I visualised a gigantic blue sound wave rippling over our milky way galaxy and it was a truly magnificent sensation. Some totally awesome music was happening in my mind and it started out of simple abstract sounds. If only I had keyboards and synths at the time!

Majestyk

I like the introverted/paranoid fellings that can come from marijuana use. I find it helpful as it promotes an introspection without ego. In that time between putting my head to pillow and falling asleep, I tend to review my behavior towards others, that day, in a more objective frame of mind. It has provoked more than one apology, the the following day, for being an ass the previous day.

lowmagnet

Then drink it!

lowmagnet

My dad said my mom smoked while I was in utero, and I'm a 'sub-genius' or 'superior intellect' by standardised IQ tests (and I like saying sub-genius because it invokes feelings of Bobness)

ps418

After reading a few other papers and a recent review of cannabis and the brain (Iverson, 2003), I found a few more interesting tidbits.

Regarding brain damage due to cannabis use: Block et al (2000) examined 18 heavy users and 13 controls with MRI and found no evidence of any regional tissue changes, contra older reports that in heavy users certain areas were atrophied. In experiments approximating chronic use in mice-- up to 250mg/kg/day for 2 years-- no histopathological changes were observed (Chan et al, 1996). For comparison, an average adult who smokes one average-potency joint per day is recieving approximately 10mg/kg/day. Claims for cannabis-induced brain damage in the 70's were based on a small number of rhesus monkies and flawed experimental designs, and subsequent rhesus studies with larger samples and higher doses found no histopathological changes (Scallet, 1991), even with high doses of smoked cannabis delivered via gas masks over 2 years.


Regarding cancer: In addition to the studies I cited on page 2 of this thread, there are some other studies showing remarkable anti-tumor effects of cannabinoids. A major one that I did not cite was one by Galve-Roperh et al (2000) showing the effects of THC injected directly into glioma tumors in the brains of the rats. The results showed not only significantly increased survival times, but complete eradication of the tumor in 20-35% of the treated rats. In humans, btw, the average time to death from gliomas, even with agressive treatment (surgery and chemotherapy), is less than one year, according to the commentary on Galve-Roperh et that appeared in the same issue of Nature Medicine.

Regarding the analgesic or anti-nociceptive properties of cannabinoids: As I said above, it is unlikely that cannabinoids will ever be widely-used as a stand-alone analgesic. However, there is good reason to think that it may be useful in combination with opioids in the treatment of chronic pain, especially neuropathic pain. In several standard tests in mammal models, cannabinoids such as THC have a synergistic effect, each enhancing the analgesic effects of the other (Cichewicz et al, 1999; Fuentes et al, 1999; Smith et al, 1998). Thus, cannabinoids may be useful to augment treatment of chronic pain, particularly is it allows for use of smaller amounts of opioids, slowing the buildup of tolerance, or if opioids alone are less than completely effective for pain management.


Refs

Block et al, 2000. Effects of frequent marijuana use on brain tissue volume and composition. Neuroreport 11(3), 491-6.

Chan et al, 1996. Toxicity and carcenogenicity of delta9THC in Fisher Rats and B6c3F1 mice. Fundam Appl Toxicology 30, 109-117.

Cichewicz et al, 1999. Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. Journal of Pharmacology and Experimental Therapeutics 289(2):859-67.

Fuentes, et al, 1999. Cannabinoids as potential new analgesics. Life Sciences 65(6-7): 675-685.

Galve-Roperh et al, 2000. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nature Medicine 6, 313-319.

Iverson, 2003. Cannabis and the brain. Brain 126, 1252-70.

Scallet, 1991. Neurotoxicology of cannabis and THC: a review of chronic exposure studies in animals. Phamacology Biochemistry and Behavior 4, 671-676.

Smith et al, 1998. The enhancement of morphine antinociception in mice by delta9-tetrahydrocannabinol. Phamacology Biochemistry and Behavior 60, 559-66.

Patrick

sweep

Corwin, I did "read the fucking article." And reread it. And I fail to see in the article where it claims that marijuana causes brain damage. Quite the contrary, actually. Especially not the "common" damage you claim, more common than that caused by alcohol, and for sure not the kind that you alluded would show up in tissue samples. Recoverable memory and perception problems, but not "brain damage" (as I think of it, anyway). Perhaps we're just working with two different preceptions of what "brain damage" is.
--------------------------------------------------------------------------------
Corwin wrote:

Marijuana users suffer from lack of energy, memory impairment, and cognative function. These are all well established in medical literature. The actual CAUSE is different, (blockage of neurotransmitters rather than cell death) but the effect is the same.

compare what corwin wrote to the quote (early in on page two of the thread) and it appears that some misunderstanding has occurred. Whether or not Corwin was aware of what he was talking about can only be verified by Corwin. It appears that his writing is ambiguous to the effect of misleading those who are attempting to understand the actions of thc and cannabis related ligands. His response seemed to imply, at least to me, that the blockage of neurotransmitters would be due to cannabinoids binding with receptor sites over the post synaptic membrane on specific neurones without activating them. According to the quote, that patrick has provided links, cannabinoids common to the CB1 receptor, ARE agonists; they bind to the CB1 receptor and activate it, even though the passage of ions through said gate lead to an overall inhibitory effect which corresponds with what corwin was striving to convey.

Corwin, it seems was right about the effects on brain activity, according to the cited article, but was careless, since his wording was demonstrably responsible for misconceptions born of those with basic neurological understanding.

QUESTION TIME:

patrick: my friend likes cannabis but he does not like the increased heart rate and, generally, the panicky feelings associated with cannabis use. What is responsible for this? Are there any forms of cannabis which lack this property? Do you know how cannabis without said properties can be achieved? sorry if I have overlooked any information you might have pointed at.

ps418

The increased heart rate is probably the result of activation of CB1 receptors in the autonomic nervous system. It is certainly at least partly mediated by CB1 receptors somewhere in the body, because in human subjects who take the CB1 receptor antagonist SR141716 two hours before smoking, there is a 59% attenuation of the HR increase (Huestis et al, 2001) yet had no effect on THC plasma concentration. The psychological effects are also mediated by CB1 receptors also, btw, so using a CB1 anatagonist would block these effects as well and thus be self-defeating. It is certainly not due merely to the smoking route of administration, since IV THC increases HR also.

How to minimize these effects? Since the HR increases (to a point) in a dose-dependent way (Perez-Reyes et al, 1982; Menkes et al, 1991), the obvious way is to reduce the dose. As I said before, I think most people take far more than they need to produce the effects they want. If someone has serious cardiac problem, I would recommend they quit altogether. For most everyone else, however, the cardiac changes should not be a big worry, since the typical HR increase is no more dangerous than a mild jog, and the large cohort study (Sidney et al, 1997) I cited earlier in the thread did not find any association between cannabis use and cardiac mortality.

There is also evidence that CBD (cannabidiol) counteracts the HR increase (Nahas and Trouve, 1985), and there is probably significant between-strain variation in proportional CBD content. So perhaps strains proportionally high in CBD would reduce the HR increase. Unfortunately this is an area where there needs to be alot more research. Most breeding has pursued yield and resin content rather than for particular cannabinoid profiles. It may be however that CBD diminishs the high as well. I don't know. Beta-blockers may also attenuate the HR increase, but I don't know if I'd take BBs just to enhance my enjoyment of cannabis.

As far as the paranoia goes, the best solution is either to quit using if the effects are bothersome (who wants to be paranoid?), and/or to be educated about the effects. Let me explain what I mean by the latter.

For many people, I think it is actually the HR increase that causes the paranoia. I think that this is partly because of the fact that the heart rate increases at the same time that one's perception of time is altered. Even without a HR increase, the cannabis high would probably lead many people to overestimate their heart rate (there are interesting experiments with rats showing that their perception of time is altered in the same way). Iverson (2003) notes:

I think that what happens is that 1) the HR increases due to CB1 activation, and 2) the perceived HR increases due to the psychological effects of THC, which can lead to 3) a further anxiogenic HR increase.

There have been several instances even in my own experience of people under the influence of LSD who were convinced that their hearts are beating waaay too fast and that they might die, yet when I took their radial pulse using a objecive clock, it is elevated only 20-30% above their baseline heart rate. The point is that because many people are not aware that their own perception of time has changed, they misjudge their own cardiac state, leading to an inaccurate but nonetheless anxiety-inducing perception that their safety is in danger.

Hope that helps.

Refs

Huestis et al, 2001. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry 58(4):322-8.

Menkes et al, 1991. Salivary THC following cannabis smoking correlates with subjective intoxication and heart rate. Psychopharmacology (Berl) 103(2):277-279.

Nahas and Trouve, 1985. Effects and interactions of natural cannabinoids on the isolated heart. Proc Soc Exp Biol Med. 180(2), 312-316.

Perez-Reyes et al, 1982. Comparison of effects of marihuana cigarettes to three different potencies. Clin Pharmacol Ther. 31(5),617-24.

ps418

Sweep, I did a little more homework on your question. Here's what I found. Regarding the effects of cannabinoids on heart rate and the cardiovascular system in general:

Grotenhermen, 2003.

So, the cannininoid increase in HR can in fact be blocked by betablockers. I don't know if bb's selectively block the HR increase, or if they also block desirable main effects as well. Its interesting also that activation of CB1 receptors can reduce vascular resistance. I wonder if the CB1 receptor has been investigated as a target for hypertension therapy?

Also, as I suggested, CBD does partly block the cannabinoid increase in HR. Unfortunately, it appears that CBD has a general antagonistic effects against THC, so increasing the CBD/THC ratio to reduce HR increase may be be self-defeating.

Grotenhermen, 2003.

Refs

Grotenhermen, 2003. Pharmacokinetics and
Pharmacodynamics of Cannabinoids. Clinical Pharmacokinetics 42, 327-360.

Karniol IG, Shirakawa I, Kasinski N, et al. Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man. Eur J Pharmacol 1974; 28 (1): 172-7

Petitet F, Jeantaud B, Reibaud M, et al. Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of ∆9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Life Sci 1998; 63.

Zuardi AW, Shirakawa I, Finkelfarb E, et al. Action of cannabidiol on the anxiety and other effects produced by delta 9-
THC in normal subjects. Psychopharmacology 1982; 76 (3):
245-50.

Patrick

ps418

Out of curiosity, I looked at the research on cannabis and driving skills. There are several ways to approach this issue. You can 1) do controlled experiments using real cars and real-world driving conditions, you can do 2) experiments with driving simulators, or you can 3) look at automobile crash statistics, considering car crashes from an epidemiological perspective. Some conclusions from this research are as follows:

1. The most obvious influence you'd want to look for is an influence on reaction time, RT. Increases in RT are expected a priori to increase the risk of accident. In Sexton et al (2000) driving simulator experiments, and many other experiments as well, cannabis did not impair RT even in the high-dose condition. Time-to-brake in response to a car-pulling out in front of them was the same as with placebo, and time to respond to green light was actually shorted than with with placebo.

2. The most consistent deficit produced by cannabis is a slightly greater amount of what is called Standard Deviation of Lateral Position (sdlp), which is basically a measure of how much lateral movement occurs within the lane. However, the level of impairment is suprisingly small compared to alcohol, fatigue and many OTC medications. Robbe (1998):

By comparison, BACs of 0.03-0.07 are legal everywhere in the US, where maximum legal BACs are 0.08-0.1. And a dose of 100-300 micrograms THC per kilogram is equal to the THC dose from one-half to one and one-half joints, which is a substantial dose (note: earlier in this thread I said an average THC dose per joint was 10mg per kg, which ws incorrect). In other studies, for instance one using a driving simulator, lane-keeping performance is even better with cannabis only, but non-additively worse in combination with alcohol. This is consistent with other studies showing that a small amont of alcohol and a small amount of cannabis impair performance much more than would be expected based on studies of each in isolation. Krüger and Vollrath (2000) found that:

3. Drivers under the influence of cannabis drive more slowly, increase their following distance, and are less likely to pass other cars. Individuals under the influence of cannabis often overestimate their level of impairment and adjust their driving to compensate. Alcohol has the opposite effect, that is, individuals under the influence of alcohol tend to underestimate their level of impairment, drive faster, decrease following distance, and pass more. Using subject self-ratings, Robbe (1998) in their study of driving under real-world conditions noted that "[a]lcohol impaired performance relative to placebo but subjects did not perceive it. THC did not impair driving performance yet the subjects thought it had," and that "[e]vidence from the present and previous studies strongly suggests that alcohol encourages risky driving whereas THC encourages greater caution, at least in experiments."

4. Because the experimental studies of cannabis' effects on driving ability do not lend themselves well to prohibitionist arguments, prohibitionists cites correlational statistics showing that THC metabolites are present in the blood of a relatively large number drivers involved in accidents. Of course, the problem with inferring that cannabis therefore causes accidents is that the vast majority of these, up to 84% in some studies (Earlywine, 2002, p. 211), alcohol is present as well. When you look strictly at accident-involved motorists positive for cannabis only, there is little evidence of increased automobile accidents. From Earlywine (2002, p. 211):

Recent reviews of crash culpability studies also fail to support a causal role for cannabis in automobile crashes. Chesher Longo (2002) state:

A 1999 review of automobile accident epidemiology also failed to support a causal role for cannabis in automobile crashes. Bates and Blakely (1999) wrote:

That strikes me as somewhat counterintuitive, though I do not doubt that cannabis typically causes an overestimation of impairment and an increase in some safe-driving behaviors such as reduced speed and increased following distance. I still recommend strongly against anyone driving while under the influence. Nevertheless, as far as the somewhat dire suggestions made by the cannabis prohibitionists go, it seems pretty obvious that they are not supported by the experimental or epidemiological evidence.

Refs

Bates and Blakely, 1999. Role of cannabis in motor vehicle crashes. Epidemiologic Reviews 21, 222-232.

Chesher and Longo, 2002. Cannabis and alcohol in motor vehicle accidents. In: F. Grotenhermen and E. Russo (Eds.) Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. pp. 313-323.

Earleywine, 2002. Understanding marijuana: A new look at the scientific evidence. Oxford; New York: Oxford University Press.

Krüger, and Vollrath, 2000. Effects of Cannabis and Amphetamines on Driving Simulator Performance of Recreational Drug Users under Natural Conditions. Presented at the 15th International Conference on Alcohol, Drugs and Traffic Safety (T2000) Stockholm, Sweden: May 22nd-26th, 2000.

Robbe, 1994. Marijuana's Effects on Actual Driving Performance.

Sexton et al, 2000. The Influence of Cannabis on Driving, Prepared for Road Safety Division, Department of the Environment, Transport and the Regions, UK, by Transport Research Laboratory, Ltd., TRL Report 477.

ps418

One more post and I promise I'll let the thread die.

I'm having some second thoughts about the effects of cannabis smoking on the lungs. I still do not think that there is good evidence that cannabis smoking causes lung cancer or other pulmonary disorders, but I'm not confident that it will not turn out to be a risk factor. Basically, my second thoughts are that while the current data is encouraging, I wouldn't want to say that cannabis smoking is harmless to the lungs, particularly at high daily levels.

The mortality data I cited (Sidney et al, 1997) is encouraging in that it showed no excess pulmonary or cardiac mortality associated with cannabis use, but the average age of the cohort was like 50 years, and it may be that a signficant effect will show up 10-20 years down the road. So it is not as definitive as my earlier comments might have suggested.

There is also a recent longitudinal study of lung function in young cannabis smokers which, while not definitive, is suggestive. Taylor et al (2002) examined lung function in a birth cohort, N=~900, at 18, 21, and 26 years. Lung function was assessed as FEV1/VC, where FEV1 is forced expiratory volume in 1 second, and VC is vital capacity, which is the total volume of air that can be exhaled in one breath. In all people, this measure declines with age. Tashkin et al (1997) examined FEV1 decline in a sample of 394 adults (131 heavy marijuana-only, 112 marijuana plus tobacco, 65 tobacco alone, and 86 nonsmoking controls) over a period of 8 years. Taskin et al found as expected that tobacco caused an accelerated decline in FEV1 with age, but not find any additive effects of cannabis with tobacco, or effects of cannabis alone on FEV1 decline. Tayler et al (2002) on the other hand found a cannabis dose-dependent decline in FEV1/VC in their sample. However, when they corrected for tobacco smoking, the effect was no longer statistically significant.

Nevertheless, I would not be surprised if longer followup nudges the result into statistical significance. We'll see.

One more thing of interest here is that I found a source supporting something I said earlier about higher potency cannabis being better for the lungs. Matthias et al (1997) examined the effets of varying cannabis potency on breathhold duration, cumulative puff volume (amount smoked), deposition of tar, delivery of THC, and carboxyhemoglobin (COHb) boost (the increase in blood carbon monoxide). The two potencies tested were 3.95% and 1.77%. Smoking was ad libidum, as much as the subject wanted. Their results indicated that 25% less tar is deposited by the higher potency. The higher potency resulted in reduced cumulative puff volume, but the results seem to indicate that even at a given CPV and breath-holding time, the higher potency results in less tar deposition.

Refs

Matthias et al, 1997. Effects of Varying Marijuana Potency on
Deposition of Tar and D-9-THC in the Lung During Smoking. Pharmacology Biochemistry and Behavior 58, pp. 1145–1150.

Taskin et al, 1997. Heavy habitual marijuana smoking does not cause an accelerated decline in FEV1 with age. American Journal Respiratory Critical Care Medicine 155, pp. 141-148.

Taylor et al, 2002. A longitudinal study of the effects of tobacco and cannabis exposure on lung function in young adults. Addiction 97, pp. 1055–1061.

Patrick