One hopes that the medicinal aspects of Marijuana can be separated from the negative impacts. I know that the straight M.J. causes significant memory impairment and sloth (personal observation…) but now there’s some more detailed study.
One must remember that the presence of a “receptor” on a cell surface for a chemical does not tell you what the receptor does. It can turn on a growth hormone, or turn it off. It can cause cell proliferation, or cell death. That there are a thousand receptors for a chemical doesn’t tell you if it does good, bad, or some of each (as a receptor can do different things on different cell types).
Even then, in the brain, there are times you WANT a bit of brain shrinkage. The brain forms by extensive wiring up, then the “pruning” of selected connections to establish the best function. Inhibition of that needed shrinkage can be as bad as too much shrinkage later on.
Marijuana Use May Shrink the Brain
Smoking Pot Could Have Lasting Effects on the Brain
By Jennifer Warner
WebMD Health News Reviewed by Louise Chang, MD
I find it refreshing that the “reviewer” is listed…
June 2, 2008 — Long-term marijuana use may actually shrink certain parts of the brain and have lasting effects on mental health.
A new study shows heavy marijuana use over several years was associated with structural differences in at least two different regions of the brain, the hippocampus and amygdala.
Researchers found that the hippocampus, which is thought to regulate memory, was an average of 12% smaller among marijuana users, compared with people who didn’t smoke pot. The amygdala, involved in emotion and memory, was an average of 7% smaller.
The study also suggests that long-term marijuana users were more likely to report symptoms associated with mental disorders, although the strength of their symptoms didn’t meet the criteria for diagnosis of mental illness.
In the study, researchers used high-resolution magnetic resonance imaging to compare the brain structure of 15 men who smoked more than five joints of marijuana daily for more than 10 years with images from 16 men who did not smoke pot.
The participants also took a verbal memory test and were evaluated for symptoms of mental disorders.
The results showed men who smoked pot regularly had significantly lower brain tissue volumes in the hippocampus and amygdala areas, as well as more symptoms of mental disorders.
Researchers say marijuana users also performed significantly worse on the verbal learning test, but these differences did not correlate with brain volumes in either group.
I observed that after a relatively short exposure interval (about a year, irregularly) it took between 6 months and year to mostly recover full memory function. I have no idea what longer term exposure or more intense exposure would do, or if it is recoverable then.
OTOH, it might be individual idiosyncratic. I know of at least two folks who smoked heavily in college and went on to get an MBA and Law Degree, respectively, from U.C. Berkeley. Both seemed to remember things fairly well. Enough to pass…
Then there is the “gender” effect
It is also different in women than in men, so gender changes the effect of the receptors too.
Gender effects on amygdala morphometry in adolescent marijuana users
Tim McQueeny,a Claudia B. Padula,a Jenessa Price,a Krista Lisdahl Medina,b Patrick Logan,c and Susan F. Tapertd,e,*
Note that the amygdala is involved both here, and in memory. One brain center, two impacts.
Adolescent developments in limbic structures and the endogenous cannabinoid system suggest that teenagers may be more vulnerable to the negative consequences of marijuana use. This study examined the relationships between amygdala volume and internalizing symptoms in teenaged chronic marijuana users. Participants were 35 marijuana users and 47 controls ages 16–19 years. Exclusions included psychiatric (e.g., mood and anxiety) or neurologic disorders. Substance use, internalizing (anxiety/depression) symptoms and brain scans were collected after 28 days of monitored abstinence. Reliable raters manually traced amygdala and intracranial volumes on high-resolution magnetic resonance images. Female marijuana users had larger right amygdala volumes and more internalizing symptoms than female controls, after covarying head size, alcohol, nicotine and other substance use (p<0.05), while male users had similar volumes as male controls. For female controls and males, worse mood/anxiety was linked to smaller right amygdala volume (p<0.05), whereas more internalizing problems was associated with bigger right amygdala in female marijuana users. Gender interactions may reflect marijuana-related interruptions to sex-specific neuromaturational processes and staging. Subtle amygdala development abnormalities may underlie particular vulnerabilities to sub-diagnostic depression and anxiety in teenage female marijuana users.
Human adolescent studies document aberrant structural morphometry among brain areas that are associated with the cognitive sequelae of marijuana . Irregularities are observed in the prefrontal cortex, hippocampus and cerebellar vermis as well as white matter organization in teenage marijuana users compared to non-using peers, and these abnormalities were associated with poorer neurobehavioral outcomes [40–44].
Gender may represent a differential risk factor for acquiring psychopathology. There is evidence which suggests female adolescent substance users experience negative consequences of drug use earlier than male peers and are more likely to suffer from an internalizing disorder whereas male substance abusers have more externalizing behaviors . The neurocognitive bases for gender-related risk factors for marijuana use and drug use consequences remain relatively unclear. Adolescent girls and boys also differ in the timing of neuromaturational sequences, hormone exposure and neuronal organization [46, 47], thus, male and female teens may be susceptible to gender-specific brain changes resulting from chronic marijuana exposure. In addition, female teens exhibit elevated CB desensitization relative to same-aged males as well as adult men and women , suggesting that the endocannabinoid may have a stronger regulatory role in girls. Therefore, marijuana-related brain changes may differ by gender through interactions with adolescent neuromaturational processes.
Specifically, smaller right amygdalas were linked to worse mood and anxiety symptomatology in the whole sample. Plotting the relationship between right amygdala volume versus internalizing symptom scores revealed that the inverse relationship between amygdala and mood/anxiety was driven by female controls and males (see Figure 3). In contrast, female marijuana users show the opposite brain-behavior pattern: larger amygdala volumes were linked to worse internalization scores. Independent of amygdala morphology, marijuana users had higher internalizing composite scores, and female marijuana users endorsed the greatest depression and anxiety symptoms.
These findings are consistent with our laboratory’s previous studies on different samples of marijuana using teens [43, 44]. For example, Medina and colleagues  reported larger prefrontal cortex volumes in female marijuana using adolescents, and larger volumes were linked to poorer executive function. Subclinical depression symptoms have also been reported in conjunction with reduced white matter volumes in teenage marijuana use , which reflects a similar pattern of neurobehavioral links with internalizing problems as in the current study. Our findings also align with previous literature connecting depression and anxiety to smaller amygdala size in both clinical samples [49, 66, 69] and in normal healthy teens . However, one study of adult marijuana users found smaller amygdala volumes  and evidence for altered amygdala morphometry in depressed samples is mixed . If replicated, these results carry important public health implications as interventions targeting teenage marijuana use may mediate risks for developing substance use disorders and comorbid internalizing problems.
Discrepancies between adult and adolescent structural MRI findings could be related to the disruption of neuromaturation by early chronic marijuana use. Brain size increases through adolescence with decreasing volumes observed over the course of adulthood . Exogenous cannabinoid administration is associated with altered astrocyte functioning, and astrocytes play a critical role in eliminating weaker connections and maintaining neuronal health [73, 74]. By interfering with these support processes, marijuana exposure during adolescence may impair typical pruning, which could ultimately result in larger regional brain volumes. Chronic exposure to marijuana may also compromise neurogenesis, as reduced levels of nerve growth factor and brain derived neurotrophic factor have also been reported among adult marijuana users [75, 76], and this effect may have a greater impact after the pruning stage is primarily complete. Taken together, marijuana use may impact brain development such that interrupted pruning (i.e., maturational delay) is followed by accelerated aging (reduced neurogenesis). Therefore, larger right amygdala volumes could be expected among adolescent marijuana users, whereas continued exposure through adulthood may be related to smaller volumes eventually .
There’s a lot more in that article. Especially about how M.J. has more effect on women than on men, that it can vary with hormonal cycles, etc. etc. FWIW, the two M.J. users who went on to success, noted above, were both post puberty males…
Overall, it looks like if you wait until after puberty, and are male, it may not be “too bad”, but use as a developing adolescent, and especially among girls, can have negative effects lasting a lifetime. Then the question becomes “Do the negatives outweigh the positives?”, which I doubt can be answered at our present level of understanding.
FWIW, this all tends to match my personal observations of M.J. prolonged users. A bit “ditzy” and more emotional. Don’t remember detail as well, and tend to emotional rather than logical fact based arguments. No, not all. There’s a lot of variation. And, frankly, some folks could benefit from being more emotional and less fact based. Many jobs don’t require a lot of long term memory and folks may not want to remember a lot of a painful life. So again, observing an effect does not tell you if it is for good or bad.
Generally, though, I’d vote for avoiding heavy use at all times, and most or all use during the developmental years. Or maybe I just don’t like the idea of something messing with my brain volume…