The original post in its native form was far too long, so I broke it up into seven different posts, in addition to this post. The separate sections are listed below. The original post, what is left of it, is here. For an examination of the evidence of whether or not cannabis causes actual structural damage to brain cells, axons or dendrites, see here. For an analysis of neuropsychological batteries of cannabis users to determine whether or not they suffer brain damage, see here. For an analysis of EEG testing of cannabis users to discover evidence of brain damage, see here. For an analysis of studies looking at cerebral blood flow in cannabis users, see here. For an admittedly impressionistic analysis of whether or not cannabis causes schizotypal symptoms in users, see here. For a summary of the findings of cannabis and brain damage, see here. LSD and psilocybin, while not causing permanent brain damage (that we know of so far), can cause HPPD (Hallucinogen Persisting Perception Disorder), a long-term perceptual disturbance of unknown etiology. I have HPPD myself from using hallucinogens about 40 times, but “suffering” from HPPD once again is an interesting concept, at least in my case. All I get are brighter colors, mostly in neon signs and store displays, and only at certain times. Maybe lots of people would love to have this effect, as the world looks so much better this way. I called up an ophthalmologist about it and he laughed me off the phone, saying he doesn’t treat people whose colors improve. It is only my continuing neurosis that causes me to view these changes as frightening instead of integrating them. LSD does have a deleterious effect on the visual system of the brain – it is hypotoxic to that area in lab animals, for instance, birds – but it doesn’t cause any generalized brain damage at all that we know of, and we have been studying LSD’s effects on the brain for about 50 years or so now. LSD does cause reductions in 5-HT2 receptors on serotonin neurons. But this is a case of these receptors retreating back into the cell due to LSD’s assault on those receptors. After about a week, the receptors to poke back out of the cell again. The most recent evidence also indicates that psilocybin (mushrooms) and mescaline (peyote) also do not cause any generalized brain damage, although psilocybin can cause HPPD. Due to the risks of HPPD, this blog unfortunately does not recommend that anyone use LSD or psilocybin even one time, unless maybe if you are dying. Ecstasy (MDMA) produces comparatively dramatic harm to the brain after only a handful of doses (2-10 doses), with the effects increasing with continued use. The drug causes degeneration of serotonergic axonal terminals, which afterwards do not grow back correctly, if at all. There are suggestions that there may be hippocampal damage. On intelligence tests there are deficits in working memory, declining vocabulary, impairments in verbal learning, associative learning and attention and increased distraction. There also seem to be some mood changes. Perfusion deficits and increased delta waves on EEG have also been found, but the same study did not find these in cannabis users. Impairments were also found in the ability to drive a car in Ecstasy users, even after they were abstinent. However, a recent study found no persistent effects from one dose of Ecstasy. Therefore, it appears that using Ecstasy one time is possibly safe. However, taking Ecstasy as few as an average of 3.2 times causes noticeable damage in verbal memory. Ecstasy should be taken no more than once in a lifetime, if at all. Evidence strongly suggests that the heavy use of PCP, ketamine and DXM may cause permanent brain damage and can often cause schizophrenia-like symptoms which may be related to that damage. The theorized damage involves the vacuolization of neurons (basically a hollowing out and death of the neuron) in various parts of the brain. The evidence comes from rat studies and the dosages have been criticized, but humans are far more sensitive to the effects of dissociatives than rats are, so the differential doses are probably about right. The rat evidence has now been challenged by monkey studies, so the matter is far from settled. But until it is, extreme caution, if not outright avoidance, seems to be the best policy for these drugs. PCP can probably be used up to a dozen or so times in life with no permanent damage. Beyond that, things get a lot touchier. Heavy users show an extremely high rate of schizophrenic and psychotic symptoms, along with symptoms of brain damage. There seems to be some recovery with abstinence, but full recovery is by no means assured. Evidence indicates that ketamine can be used at least once with no permanent consequences at all to the brain. Beyond that, it is up in the air. Ketamine can surely be used at least a dozen times with no risks to the brain. Beyond that, things get hazier. Heavy DXM users have reported a very high rate of psychosis and schizophrenia-like symptoms, along with symptoms of organic brain damage. Users should approach DXM use with caution, and heavy use should be ruled out. Heavy methamphetamine use has been proven to cause permanent damage to dopaminergic systems, especially in the striatum, caudate and putamen (at ½ gram a day, 5 days a week, and 2 years of use). Studies have also shown degeneration of axons on serotonergic neurons and loss (cell death) of up to 15 In the study above, there was some recovery of the dopaminergic system with abstinence, but it was only partial. Meth can probably be used a dozen or so times without any permanent damage. Beyond that, no guarantees. There is some suggestive evidence of chronic psychosis, depression and anxiety directly related to heavy methamphetamine use (over 10 years of heavy use). Impairments in learning, processing speed, and working memory, along with delayed recall, are found in meth users. Brain dysfunction is often readily apparent in heavy meth users. This is one category of drug user, in contrast to most other drug users, that does sometimes appear “fried.” Much of this “fried” appearance seems to clear up with abstinence. Methamphetamine can probably be used up to a dozen times or so in moderation without any permanent consequences to the brain. Nevertheless, some users have reported permanent effects from only 2-3 weeks of very heavy use. Meth is nasty stuff, and it’s best to keep away from it. Heavy drinking can depress neurons for up to two years. With continued heavy drinking, at some point, there is organic damage, which in many cases is permanent, although there is often significant recovery with abstinence. The case of the “wethead” and “dry drunk,” the former alcoholic who is still damaged, psychologically or cognitively, is well known. Heavy use of barbiturates over many years causes a damage syndrome that looks like chronic alcoholism and that does not completely recover with abstinence. Even chronic Valium use causes long-term EEG changes of unknown significance. Sniffing glue has been proven to be possibly the worst thing you can do to your brain short of putting a bullet in it, and the effects do not recover completely with abstinence. Cocaine, unfortunately, seems to be capable of causing brain damage with as few as 11 doses (constriction of vessels in the brain). At three years of using several times a week, there is slowing on the P300 event related potentials test, that may not recover fully with abstinence. Recent studies have also shown that chronic heavy cocaine use causes reductions in gray matter in various parts of the brain. This means that heavy cocaine use causes an actual loss of brain cells in parts of the brain. It may also cause white matter reductions, which means a loss of connections in the brain. There are also impairments in attention, learning, memory, reaction time and cognitive flexibility in cocaine users. It is not known whether these clear up with abstinence. This blog recommends that lifetime use of cocaine be limited to 10 times or less. Even there, there is a slight risk of sudden death due to perturbations in the heart’s electrical rhythms. These perturbations can cause a sudden heart attack or even possibly a stroke. Vasoconstriction is probably involved. In many of the above cases, there is some recovery with abstinence, but often not to the previous level. Experimental use of PCP, ketamine, cocaine and methamphetamine (use up to a dozen or so times for each one) probably does not cause significant permanent damage. Beyond that, you play with matches. Compared to other drugs of abuse, such as Ecstasy, PCP, Ketamine, DXM, cocaine, methamphetamine and alcohol, the effects of cannabis on the brain are dramatically less deleterious. In terms of its effects on the brain for heavy users, cannabis is surely by far least damaging intoxicant of them all, for what that is worth.