I. Preface

I recently posted an article (Part I) in which I proposed a hypothetical scenario, in which an individual who is offered marijuana takes time out to research the drug exclusively through recent articles on PubMed to see if its a good idea or bad idea. It was meant more as an intellectual exercise, not a commentary or piece of advocacy for either side of the legalization debate (although the commentary after quickly delved into that debate). I wrote the article for the following reasons:
1. It seemed like a cool idea at the time. 
2. I don't know very much about the science of marijuana, but I have a neuroscientific and policy-based interest in the topic.
3. I am interested in how internet search criteria can influence perception and belief on different topics.
4. I wanted to explore the usefulness of using current peer-reviewed research in making life decisions, since peer-reviewed research is widely considered (I think) our purest source of scientific fact. 

Posting of the article resulted in a fascinating and wide-ranging commentary about the topic of cannabis, which obviously engenders a lot of strong opinions. From the comments, three main questions/concerns seemed to come up in response to what the article actually said.

1. In the article, the finding was that the language describing the effect of THC on users in the newest and most accessible literature was very negative. But the regular claim of cannabis users, and the implication of its widespread recreational use, indicate that its use has a positive effect. The discrepancy merits an explanation.
2. The claim was made that multiple commissions and reports have called for a release of restrictions on marijuana use, based in part on their relative safety, but that these are regularly ignored. This claim merits investigation because, if it is true, then those claims should alleviate concerns for an individual who wants to try it.

3. It was implied that studies of the effects of THC in lab settings will trend more negative because there is something inherently scary and paranoia-inducing about labs and researchers. The descriptions would be different if the tests were done on beautiful mountaintops or on a sunny beach.

Herein, I will try to answer the first two issues. I doubt that I'll find much on the third. In keeping with the spirit and structure of the original article, I will continue to search exclusively in primary source material, but I will expand my search to include official commission and government documents on the topic. For those of you who might want to continue this in the fictional vein of the first article, here you go:

"Jimmy meets up with his friend, who we will call Freddy. Jimmy tells Freddy that he consulted PubMed, and based on what he read, smoking pot sounded like a bad idea. Freddy is amazed and confused, because he really enjoys it. So they decide to go back to Jimmy's computer to dig some more, because neither one could tolerate an unanswered question or logical discrepancy."

II. The Positive and Negative Effects of THC

When I started this most recent search, I first found a lot of articles about brain differences in the fMRIs of people who responded differently to 10 mg oral THC (the key differences seem to be the parahippocampal gyrus, medial temporal cortex and cerebellum). Interesting, but not helpful unless Jimmy wants a pre-cannabis MRI. Descriptions of the effects of THC in those papers were identical to those in previous articles: "acute psychosis, increase in measures of anxiety, sedation and intoxication," with no mention of whether or not the subjects liked it.

After a search that led me through reports by Zvolensky et al (2009, 2010) about increased risk of panic disorder in marijuana users, I found the much more helpful Thomas 1996. In this survey, "light" marijuana users (less than 50 times total) reported that 20% experienced panic attacks, 13% reported psychosis ("strange, unpleasant experiences...hearing voices...paranoia...sense of persecution"), 6% reported their physical health harmed at some point in the history of their use. Across light and heavy users, the risk of panic attacks was significantly greater in women, by 2:1. Of course, all the risk measures go up in heavy users. So based on the survey, the odds of something bad happening (paranoid psychosis or panic) with light users is about 1 chance in 6. The study was done in New Zealand, so you have to take into account differences in hobbit consumption, etc.

After some more hopping, I was led to an excellent review by Johns 2001 that had some interesting things to say about post-cannabis "acute toxic psychosis". It quoted several international studies in which "appreciable" numbers of people were presenting with  psychotic symptoms post-cannabis. The symptoms were "mild impairment of consciousness, distorted sense of passage of time, dream-like euphoria, progressing to fragmented thought processes and hallucinations, generally resolving within a week of abstinence". 

Now we're getting somewhere. So, when scientists use the term "psychosis" (which I think anyone will admit is not a pleasant term), it can mean different things. It can be really unpleasant (paranoia, persecution complexes) or it can be pleasant (dream-like euphoria). 

In the most thorough description of the effect that I found, The National Commission on Marihuana (see Part III) gives the following detailed description: "The closest non-drug approximation may be the altered state of consciousness experienced in the hypnotic trance or transcendental meditation or the, transition zone between waking and sleep (Weil, 1971). ... at low doses (usually smoked dose about five mg. THC) include euphoria, with restlessness and mild mental confusion. Sensory perception of the external environment is altered. Users often perceive an overestimation or slowing of elapsed time.... Visual alterations reported are more vivid imagery and seeing forms and patterns in objects that are usually amorphous. Increased awareness of subtle qualities of sound such as purity, distinctness or rhythm are characteristically perceived by users. A dreamy, relaxed state and disinhibition, with uncontrollable laughter is reported and users often believe that interpersonal relations are altered, and act to potentiate social interaction. At moderate doses intensifications of changes experienced are reported. Users' reports include disturbed associations, dulling of attention, vivid visual imagery, fixed ideas, rapidly changing positive and negative emotions, fragmentation of thought, flight of ideas, impaired immediate memory, altered sense of identity, increased suggestibility and a feeling of enhanced insight. At higher doses, interpersonal relations are dulled and the user feels less social and more withdrawn. At larger doses psychotomimetic (hallucinogenic-like) phenomena are experienced in a wavelike fashion. These include distortion of body image, depersonalization, visual illusions and distortions, synesthesia, dream-like fantasies and vivid hallucinations."

In conclusion, the gap between the way scientists describe the effect of THC and the way users describe it is a matter of purpose, and a matter of definitions. In modern papers, the description of a "high" is expected to be understood by readers, so it never makes it into the description of THC effects. Rather, the effects are stated in medical terms only, based on psychiatric definitions. Thus, it isn't a "high". It's a "psychotic event". And "psychotic" seems to have a floating definition in some cases (as might "anxiety", which is, interestingly, described often by scientists but rarely mentioned in the user descriptions).  The relative prevalence of bad things happening while on cannabis for short-term users is somewhere between 10-20%, perhaps higher for women then men. Now that the risk has been quantified and defined, Jimmy and Freddy can now make more informed decisions. Way to go, guys!

III. Commissions and Official Stances

Below are direct quotes on marijuana policy by authoritative agencies.  in case you don't want to read them, here's a summary: All federal government agencies are strongly opposed to legalization, but recognize that there are chemicals in it that could have medical application and recommend that these chemicals be studied under tightly controlled conditions. Official reports suggest that it be decriminalized and administered by doctors. All the statements discourage its recreational use and discourage its non-supervised medical use by individuals.

Office of National Drug Control Policy (via Whitehouse.gov 2012): "Marijuana and other illicit drugs are addictive and unsafe especially for use by young people.  As officials with the National Institute on Drug Abuse state, drug addiction is a progressive disease and the earlier one starts, the more likely are the chances of developing a substance use disorder...Although, some of the individual, orally-administered components of the cannabis plant ... have medical value, smoking marijuana is an inefficient and harmful method for delivering the constituent elements that have or may have medicinal value... To date, the FDA has not found smoked marijuana to be either safe or effective medicine for any condition...Furthermore, the Administration opposes drug legalization.  Legalization  threatens public health by increasing availability of drugs and undermining prevention activities. It also hinders recovery efforts and poses a significant health and safety risk to all Americans, especially our youth. Marijuana is a harmful drug and its use should be prevented and treated – not promoted."

National Institute of Drug Abuse (letter by Nora Volkow 2012)The use of marijuana can produce adverse physical, mental, emotional, and behavioral effects. It can impair short-term memory and judgment and distort perception. Because marijuana affects brain systems that are still maturing through young adulthood, its use by teens may have a negative effect on their development. And contrary to popular belief, it can be addictive.  We hope that this Research Report will help make readers aware of our current knowledge of marijuana abuse and its harmful effects.

Federal Drug Administration (given in 2006, updated in 2009): "...continues to support that placement and FDA concurred because marijuana met the three criteria for placement in Schedule I under 21 U.S.C. 812(b)(1) (e.g., marijuana has a high potential for abuse, has no currently accepted medical use in treatment in the United States, and has a lack of accepted safety for use under medical supervision). Furthermore, there is currently sound evidence that smoked marijuana is harmful. A past evaluation by several Department of Health and Human Services (HHS) agencies, including the Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA) and National Institute for Drug Abuse (NIDA), concluded that no sound scientific studies supported medical use of marijuana for treatment in the United States, and no animal or human data supported the safety or efficacy of marijuana for general medical use. There are alternative FDA-approved medications in existence for treatment of many of the proposed uses of smoked marijuana."

American Medical Association (from 2009 report): Results of short term controlled trials indicate that smoked cannabis reduces neuropathic pain, improves appetite and caloric intake especially in patients with reduced muscle mass, and may relieve spasticity and pain in patients with multiple sclerosis.  However, the patchwork of state-based systems that have been established for “medical marijuana” is woefully inadequate in establishing even rudimentary safeguards that normally would be applied to the appropriate clinical use of psychoactive substances.  The future of cannabinoid-based medicine lies in the rapidly evolving field of botanical drug substance development, as well as the design of molecules that target various aspects of the endocannabinoid system.  To the extent that rescheduling marijuana out of Schedule I will benefit this effort, such a move can be supported.

The Report on the National Commission on Marihuana and Drug Abuse,1972: (From medical policy statement) Looking only at the effects on the individual, there, is little proven danger of physical or psychological harm from the experimental or intermittent use of the natural preparations of cannabis, including the resinous mixtures commonly used in this country. The risk of harm lies instead in the heavy, long-term use of the drug, particularly of the most potent preparations.The experimenter and the intermittent users develop little or no psychological dependence on the drug. No organ injury is demonstrable.Some moderate users evidence a degree of psychological dependence which increases in intensity with prolonged duration of use. Behavioral effects are lesser in stable personalities but greater in those with emotional instability. Prolonged duration of use does increase the probability of some behavioral and organic consequences including the possible shift to a heavy use pattern.The heavy user shows strong psychological dependence on marihuana ... Organ injury, especially diminuation of pulmonary function, is possible. Specific behavioral changes are detectable. All of these effects are more apparent with long-term and very long-term heavy use than with short-term heavy use. (From "Other Recommendations"Recommends that the voluntary sector be encouraged to take an active role in support of our recommended policy of discouraging the use of marihuana.  (From Final Comments:) Considering the range of social concerns in contemporary America, marihuana does not, in our considered judgment, rank very high. We would deemphasize marihuana as a problem.

The National Academies Study: Marijuana and Medicine 1999. It's so long that you should probably  Read it yourself. Basically it sees potential in marijuana in medicine and recommends dropping to Schedule 2 level, and cites restrictions on marijuana as a barrier to its development as a legitimate medical drug. Here's a snippet from page 126: "Marijuana is not a completely benign substance. It is a powerful drug with a variety of effects. However, except for the harm associated with smoking, the adverse effects of marijuana use are within the range tolerated for other medications. Thus, the safety issues associated with marijuana do not preclude some medical uses...Three factors influence the safety of marijuana or cannabinoid drugs for medical use: the delivery system, the use of plant material, and the side effects of cannabinoid drugs. (1) Smoking marijuana is clearly harmful, especially in people with chronic conditions, and is not an ideal drug delivery system. (2) Plants are of uncertain composition, which renders their effects equally uncertain, so they constitute an undesirable medication. (3) The side effects of cannabinoid drugs are within the acceptable risks associated with approved medications. Indeed, some of the side effects, such as anxiety reduction and sedation, might be desirable for some patients. As with many medications, there are people for whom they would probably be contraindicated."