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LONG TERM USE EFFECTS & Cannabis Studies


Long term cannabis use "increases the risk of psychosis in people with certain genetic or environmental vulnerabilities", however marijuana does not cause psychosis.

Science & Research

2012 - Study ~ Assessing topographical orientation skills in cannabis users.

2012 - Study ~ Evaluation of the safety and tolerability profile of Sativex: is it reassuring enough?

2012 - Study ~ Chronic Cannabis Abuse, Delta-9-tetrahydrocannabinol and Thyroid Function.

2012 - News ~ Pot smoking not tied to middle-age mental decline

2012 - News ~ One Joint a Week for 49 Years Doesn’t Harm Lungs, Research Finds

2011 - Study (deceptive title) ~ Scientific Opinion on the safety of hemp (Cannabis genus) for use as animal feed

2011 - Study ~ Marijuana use among older adults in the U.S.A.: user characteristics, patterns of use, and implications for intervention

2011 - Study ~ Popular intoxicants: what lessons can be learned from the last 40 years of alcohol and cannabis regulation?

2011 - Study ~ The histopathology of drugs of abuse

2011 - News ~ 125 Year Old Woman Claimed Smoking Cannabis Everyday Was Her Secret to Long Life

2010 - Study - Effects of cannabis on lung function: a population-based cohort study

2009 - Study - The morphology of the immune system in opiomania, cannabism, and polynarcotism

2009 - Study ~ Protracted cannabinoid administration elicits antidepressant behavioral responses in rats: role of gender and noradrenergic transmission.

2007 - Study - Long term marijuana users seeking medical cannabis in California
2006 - Study ~ Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis

2005 - Study - Survey of Australians using cannabis for medical purposes

2005 - Study ~ Using Marijuana in Adulthood: the Experience of a Sample of Users in Oklahoma City.

2003 - News ~ Heavy Marijuana Use Doesn't Damage Brain

2003 - News ~ Minimal Long-Term Effects Of Marijuana Use Found In Central Nervous System By UCSD Researchers

2002 - Study - Chronic Cannabis Use in the Compassionate Investigational New Drug Program: An Examination of Benefits and Adverse Effects of Legal Clinical Cannabis

2002 - Study ~ The pharmacologic effects of daily marijuana smoking in humans

2002 - Study ~ Cognitive Measures in Long-term Cannabis Users.

2001 - Study ~ Neuropsychological Performance in Long-term Cannabis Users

1998 - Study - Long term cannabis use: characteristics of users in an Australian rural area

1997 - News - Long-Term Marijuana Users Suffer Few Health Problems, Australian Study Indicates

1997 - News ~ Regular Marijuana Users Have No Higher Rates Of Mortality, Long-Term Study Concludes

1983 - Study - Neuropsychological Performance in Long-term Cannabis Users

1981 - Study ~ Cognition and Long-Term Use of Ganja (Cannabis)

1976 - Study ~ Physical assessment of 30 chronic cannabis users and 30 matched controls.

Neuropsychological Performance in Long-term Cannabis Users

Harrison G. Pope, Jr, MD; Amanda J. Gruber, MD; James I. Hudson, MD, SM; Marilyn A. Huestis, PhD; Deborah Yurgelun-Todd, PhD
Vol. 58 No. 10, October 2001
Archives of General Psychiatry. 2001;58:909-915.


Background: Although cannabis is the most widely used illicit drug in the United States, its long-term cognitive effects remain inadequately studied.

Methods: We recruited individuals aged 30 to 55 years in 3 groups: (1) 63 current heavy users who had smoked cannabis at least 5000 times in their lives and who were smoking daily at study entry; (2) 45 former heavy users who had also smoked at least 5000 times but fewer than 12 times in the last 3 months; and (3) 72 control subjects who had smoked no more than 50 times in their lives. Subjects underwent a 28-day washout from cannabis use, monitored by observed urine samples. On days 0, 1, 7, and 28, we administered a neuropsychological test battery to assess general intellectual function, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information. Test results were analyzed by repeated-measures regression analysis, adjusting for potentially confounding variables.

Results: At days 0, 1, and 7, current heavy users scored significantly below control subjects on recall of word lists, and this deficit was associated with users' urinary 11-nor-9-carboxy-D9-tetrahydrocannabinol concentrations at study entry. By day 28, however, there were virtually no significant differences among the groups on any of the test results, and no significant associations between cumulative lifetime cannabis use and test scores.

Conclusion: Some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use.

From the Biological Psychiatry Laboratory, McLean Hospital, and the Department of Psychiatry, Harvard Medical School, Belmont, Mass (Drs Pope, Gruber, Hudson, and Yurgelun-Todd); and the Intramural Research Program, National Institute on Drug Abuse, Baltimore, Md (Dr Huestis).

Corresponding author: Harrison G. Pope, Jr, MD, McLean Hospital, Harvard Medical School, 115 Mill St, Belmont, MA 02478.

 Harrison G. Pope, MD, MPH

  • Harvard title: Professor of Psychiatry
  • McLean title: Psychiatrist; Director, Biological Psychiatry Laboratory
  • Email:
  • Telephone: 617-855-2911
  • Fax: 617-855-3585
  • Office Address: Biopsychiatry Research Program
  • Degree(s):
    • 1969 BA Harvard College
    • 1972 MPH Harvard School of Public Health
    • 1974 MD Harvard
  • Residency:
    • 1977 McLean
  • Board Certifications(s):
    • 1980 American Board of Psychiatry and Neurology
  • Clinical Interests:
    1. Substance abuse, especially anabolic steroids, marijuana, hallucinogens, "ecstasy"
    2. The "repressed memory" and "recovered memory" controversy
    3. Biological treatment of psychiatric disorders


Long term marijuana users seeking medical cannabis in California

Thomas J O'Connell1* and Ché B Bou-Matar

Harm Reduction Journal 2007, 4:16 doi:10.1186/1477-7517-4-16

The electronic version of this article is the complete one and can be found online at:

Received:29 April 2007
Accepted:3 November 2007
Published:3 November 2007

© 2007 O'Connell and Bou-Matar; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Cannabis (marijuana) had been used for medicinal purposes for millennia. Cannabinoid agonists are now attracting growing interest and there is also evidence that botanical cannabis is being used as self-medication for stress and anxiety as well as adjunctive therapy by the seriously ill and by patients with terminal illnesses. California became the first state to authorize medicinal use of cannabis in 1996, and it was recently estimated that between 250,000 and 350,000 Californians may now possess the physician's recommendation required to use it medically. More limited medical use has also been approved in 12 additional states and new initiatives are being considered in others. Despite that evidence of increasing public acceptance of "medical" use, a definitional problem remains and all use for any purpose is still prohibited by federal law.


California's 1996 initiative allowed cannabis to be recommended, not only for serious illnesses, but also "for any other illness for which marijuana provides relief," thus maximally broadening the range of allowable indications. In effect, the range of conditions now being treated with federally illegal cannabis, the modes in which it is being used, and the demographics of the population using it became potentially discoverable through the required screening of applicants. This report examines the demographic profiles and other selected characteristics of 4117 California marijuana users (62% from the Greater Bay Area) who applied for medical recommendations between late 2001 and mid 2007.


This study yielded a somewhat unexpected profile of a hitherto hidden population of users of America's most popular illegal drug. It also raises questions about some of the basic assumptions held by both proponents and opponents of current policy.


Development of standardized interview

The early discovery that nearly all applicants had tried (initiated) cannabis, alcohol, and tobacco during adolescence eventually led to selection of a standardized clinical interview (SCI) as the optimum way to obtain the basic information required to assess their past use of cannabis.

Data gathered using a prototype of the SCI to screen 622 consecutive new applicants between July 1 and December 31, 2002 were analyzed in a simple relational database. Results were later reported at a May 2004 meeting and eventually published in 2005 [1]. Meanwhile, the original questions, in somewhat modified form, have been used to screen all new applicants including those seeking annual "renewals," from January 2003 on. Thus 199 of 951 (21%) of those originally screened with less searching examinations while the SCI was being developed, eventually served as their own controls. Their responses confirmed that they shared the same general characteristics as the others and also that the sensitive information sought would be provided only if specifically requested. In late 2005 a more sophisticated relational database was created and later customized with drop-down menus to allow responses to be entered directly into a laptop computer in real time, thus incorporating the database as an intrinsic part of the medical record.

Selection of areas of interest

Once the linkage between cannabis, alcohol, and tobacco had been appreciated, questions focusing on initiation and subsequent use of all three drugs were asked of several hundred consecutive applicants. The further discovery, that many had tried other "drugs of abuse" was explored by adding questions requiring yes-no responses about their initiations of 8 specific illegal agents. When patterns in personal histories suggested that family relationships and school experiences had also played a significant role in their adolescent drug initiations, the inquiry was broadened to include those areas. A prototype of the standardized clinical interview (SCI) became ready for clinical use by July 1, 2002.



4117 individual applicants were seen on as many as four occasions between November 2001 and June 30, 2007. All were seeking a physicians' approval of their use of cannabis; 3187 (77.4%), were male, ranging in age from 16 to 91 when first seen (median age 31). 930 (22.6%) were female, ranging in age from 16 to 89, with a median age of 36. The median age of the entire population was 32, reflecting both the smaller number of females and their somewhat greater age when first seen.

Table 1 shows race/ethnicity for the entire population. Analysis by year-of-birth (Table 2) reveals more Asians and Hispanics among the younger applicants, reflecting the two groups that have been immigrating to California in the greatest numbers in recent years. Analysis by both age and race also revealed other differences.

Table 1. Race/ethnicity of entire population (N = 3515). As subsequently shown by a more searching analysis, the composition of the applicant population has been changing steadily.

Table 2. Cohort analysis of race/ethnicity (N = 3185). Analysis of racial composition by year of birth cohorts also shows that the applicant population has reflected immigration trends.

Tables 3 and 4 summarize educational and occupational histories; Table 5 provides data on applicants who were unemployed when first seen. Overall, this population exhibited lower High School drop out rates and higher percentage of graduates than national averages. The percentages earning Bachelors' degrees and Doctorates are nearly identical to the national average, but only about one half as many had earned Masters' degrees.

Table 3. Highest Education Attainment over 25, Applicants compared to US Population (N = 936). In general, cannabis applicants compared favourably with national averages.

Table 4. Occupational divisions for employment for applicants and US population (N = 2092). The two groups are quite similar with the exception of Construction and Extraction, Office and Administrative Support, which are gender specific professions.

Table 5. Non-occupational divisions for applicants and US population (N = 494) The two groups are quite similar except for the relative scarcity of retirees in the applicant population.

Their occupations resembled US averages in some employment areas and were quite different in others (Table 4); in terms of non-occupational divisions (Table 5), a much smaller percentage are retirees, a finding that reflects both their relative youth and the paucity of applicants born before 1946.

Although the extremes of applicant age ranged from 16 to 91, only 3 were under 18 when first seen. The great majority (84.16%) were between 21 and 60, a finding further emphasized when the population is examined by year of birth (Table 6), a perspective that also discloses how few (4.53%) had been born before 1946. The overall male female ratio was nearly four to one (Table 7); however when examined as year of birth cohorts, it varies from over 5:1 for the youngest applicants to almost 3:1 for the oldest. Nearly 70% were Caucasians and 16% were Black, with sizable numbers of Hispanics and Asians (Table 1).

Table 6. Distribution by year of birth cohorts (N = 3946). This further emphasizes that one's birth cohort determines what drugs one can try during adolescence.

Table 7. Birth cohorts and gender (N = 3906). Although women were outnumbered by men in each cohort, there were significant differences noted with age.

Initiation and use of cannabis

An overwhelming majority (87.9%) of 3038 applicants queried about the details of their cannabis initiation had tried it before the age of 19, usually in the company of older siblings, cousins or peers. After subtracting those born before 1946, the percentage of applicants who had tried marijuana before the age of twenty went up to 90%. Some became regular users almost immediately, while others remained sporadic users for years (that interval was estimated by asking them when they first began to "buy their own").

Amounts and patterns of cannabis use

Essentially all applicants queried about their current use were consuming inhaled cannabis on a regular basis in amounts that varied considerably, but tended to remain stable over time. The range is from less than one sixteenth ounce per week to over one ounce, with about 70% estimating they consume between 1/8 and 1/4 oz./week. Almost 90% acknowledge daily, or near daily ("six days a week") use, with about 10% insisting their use is far less frequent, in the range of two to five days/week.

Mode of cannabis use

There was a decided preference for inhaled cannabis. Most had not tried edibles until their own recommendation, or that of a friend, gave them access to edibles from a club or dispensary. Only 50 of 830 (6%) questioned about edibles were using them on a regular basis. The reasons given were that edible effects were more difficult to control and more likely to be undesirable and/or prolonged.

Initiation and use of tobacco and alcohol

One of the more significant patterns revealed by comparing average initiation ages for cannabis, alcohol and tobacco within the context of birth cohorts was that the oldest Baby Boomers had tried cannabis at a considerably later age than their younger successors. By 1975, less than ten years after the "Summer of Love," in 1967, cannabis was being initiated by over half of all American adolescents at close to the same average ages they also were trying alcohol and tobacco (Table 8, Figure 1).

Table 8. Average initiation ages for entry level agents (N = 2498). This table is depicted by Figure 1 and emphasizes the rapid fall in age at initiation of cannabis after it first became available in high schools.

thumbnailFigure 1. Average initiation age tobacco, alcohol and cannabis. Those born before 1940 were fewest in number; they had also tried cannabis at the oldest average age. Baby Boomers born after 1946 were the first large cohort, and their successors were still younger when they tried cannabis. The 61–65 cohort initiated cannabis, alcohol, and tobacco at essentially the same average age.

Essentially all applicants also admitted to trying alcohol. Nearly two thirds (64.3%) of the 1226 specifically queried about alcohol blackouts had experienced at least one and 6.26% admitted to four or more. Of 1214 applicants asked to compare their current alcohol consumption with their previous lifetime peak, 130 (10.7%) claimed to be abstinent, 341 (28%) said they were drinking less than 5% of their lifetime peaks, and an overwhelming 1058 (87%) claimed to be drinking less than half as much. Most of those who noted little change from their lifetime peaks had been moderate drinkers to begin with. This is evidence that once cannabis was established as their drug of choice, this population's subsequent alcohol consumption diminished; both collectively, and as individuals, a finding that clearly deserves further evaluation.

A history of cigarette initiation, later followed by chronic use, was prevalent in this population. 2559 of 2741 (96.4%) applicants, when asked if they had ever tried inhaling a cigarette, had done so; of 1324 who were specifically queried about their lifetime cigarette use, 872 (65.8%) had become daily smokers for some length of time. Although all but four of those still smoking claim they want to quit, only 316 (36.2%) of all smokers (23.9% of respondents) had been able to do so by the time of the interview. Most who are still smoking have reduced their daily cigarette consumption; a majority relate temporary increases in their daily cigarette use to "stress." Thus the impact of daily cannabis use on cigarette consumption, although less impressive than is the case with alcohol, also seems significant and worthy of further exploration.

Other drug initiations

When examined from the standpoint of both year of birth (YOB) cohorts and admitted initiations of other illegal agents (Table 9, Figure 2) noticeable and consistent differences are revealed: whites in every age cohort had consistently tried all other illegal agents more frequently than other racial groups (Table 10).

Table 9. Initiation rates for other illegal drugs by YOB cohorts (N = 2364). With the exception of "magic mushrooms," and ecstasy (a psychedelic made illegal in 1988), initiation rates for all Schedule One drugs have declined since 1975.

Table 10. Initiations of other illegal drugs by race (N=2400). Although race seems related to initiation rates throughout, this shows that drug initiations by all aces trying cannabis have been falling proportionately as the adolescent market matured.

thumbnailFigure 2. Other illegal drugs tried by 10 year cohort analysis. Interestingly, while all cohorts sampled other illegal drugs aggressively during adolescence, the rates at which they've done so have fallen progressively. Note also the striking generational differences in peyote/mescaline initiations by older cohorts and ecstasy by younger ones.

Further cohort analysis of this population's adolescent interest in other illegal drugs, plus its nearly universal initiation of alcohol and tobacco, suggest that while race (Table 10), and generation (Table 9) exert significant influences, gender merely parallels ethnicity (Table 11).

Table 11. Initiations of Other Illegal Drugs by Gender (N=2464). Similarly, although women consistently tried all agents somewhat less often than men, the close parallels and internal consistency suggests the data are reliable.

Despite such differences (Tables 9 &10), all cohorts and racial groups have shown steady downward trends in their initiation of all other illegal drugs, with the interesting exception of psychedelic mushrooms (psilocybin) and, perhaps, ecstasy (MDMA).


It has long been recognized that users of illegal drugs may be difficult to identify, let alone recruit into a study. That chronic users of cannabis would seek medical evaluations and be so willing to share sensitive personal information within the context of their required evaluations was the unanticipated benefit of Proposition 215 that made this study possible.

Birth cohort analysis of the average ages at which applicants reported first trying alcohol, tobacco and cannabis (Table 8, Figure 1) demonstrates that a surge in youthful marijuana use began in the US in the mid Sixties. However, that event was not documented until publication of the first Monitoring the Future (MTF) data in 1975 demonstrated that over half of American adolescents were trying marijuana while still in High School.

Close questioning of applicants suggests that the majority had been motivated by a mix of physical and emotional symptoms which had been experienced at varying times in their lives. Further, that a majority had become initiates, and later chronic users of cannabis under circumstances that suggest that it was for relief of emotional symptoms in most instances. Their discovery (usually later), that cannabis also relieved physical symptoms, was most frequently made within a context of established chronic use. That notion is further supported by recent literature indicating that phytocannabinoids, newly discovered endocannabinoids, and synthetic cannabinoid agonists all seem to manifest anxiolytic effects in both humans and animals.

More than 85% of applicants had tried other illegal drugs, principally lysergic acid diethylamide (LSD), psilocybin, cocaine, and/or MDMA. The majority of those doing so hadn't remained chronic users of any except cannabis. While a majority have continued to use alcohol occasionally, the volumes consumed and the occurrence of events related to alcohol excess have sharply diminished.

A "gateway" hypothesis had developed from observations that most marijuana users studied in the early Seventies were adolescents and young adults who had first tried alcohol and tobacco; also that many had tried marijuana before later trying heroin. However, subsequent efforts to establish a definitive causal link between marijuana and "harder" drugs have been largely unsuccessful. More recently, a theoretical alternative was shown to provide an explanation for accumulated MTF data that is at least as coherent.

A significant percentage of male applicants under 30 had been treated or evaluated for treatment with Ritalin or other stimulants for attention deficit hyperactivity disorder (ADHD) as children and their histories of a preference for morning use of minimal amounts strongly suggest that inhaled cannabis enhances their ability to concentrate. The statement of one, a construction company estimator, was revealing: "after two hits (of marijuana), and my morning coffee I'm the best estimator in the company." Another, a dental technician, stated that, when I first look at my workbench, I think I'll never finish, but after a couple of tokes (of marijuana), I'm through (with work) by two o'clock." Thus, reduction of work related anxiety seems a major factor in deciding to apply for legalized use of cannabis.


Analysis of the demographic and social characteristics of a large sample of applicants seeking approval to use marijuana medically in California supports an interpretation of long term non problematic use by many who had first tried it as adolescents, and then either continued to use it or later resumed its use as adults. In general, they have used it at modest levels and in consistent patterns which- anecdotally- often assisted their educational achievement, employment performance, and establishment of a more stable life-style. These data suggest that rather than acting as a gateway to other drugs, (which many had also tried), cannabis has been exerting a beneficial influence on most.

Anecdotal evidence from repeated clinical contacts, and other data gathered incidentally over five years of experience with this population suggests that, except for very modest alcohol consumption and obligatory (addictive) use of tobacco by those trying to quit, cannabis is the only drug used past the age of twenty-five by most. Indeed, their total drug use histories suggest that by competing successfully with other, potentially more harmful agents, cannabis may have actually been protective. Evidence from federal agencies confirms that, since 1970, there has been a gradual decrease in consumption of both tobacco and alcohol (with correlated improvements in health outcomes) even as cannabis initiation by adolescents has remained at significant levels and overall chronic use by adults has been rising steadily.

While this is a self-selected sample (which restricts the generalizations that can be made from the observations reported), its large size, the consistency of the patterns uncovered, as well as their alcohol and tobacco outcomes, seem significant. For the majority, cannabis can be seen as an effective anxiolytic/antidepressant, performing as well or better than many currently available pharmaceutical agents prescribed for the same symptoms. This finding lends important support to the concept of allowing cannabis to be used medically by all those who have been chronic users and found it beneficial.


Attention deficit hyperactivity disorder (ADHD)

Cannabis (Marijuana)

Cocaine (Coke)

Ecstasy (MDMA)

Lysergic acid diethylamide (LSD)

Monitoring the Future (MTF)

Peyote/mescaline (P/M)

Psychedelic mushrooms (Psilocybin)

Standardized clinical interview (SCI)

Tokes (Marijuana)

Year of birth (YOB)

Authors' contributions

TJO conceived the study, designed it, conducted all the clinical interviews, and wrote the report.

CBB designed the relational data-base for data analysis and later modified it to serve as medical record since December 2005. Conducted statistical analysis of data and contributed several other valuable suggestions and helped write and edit the report.


Robert Field: Provided funding for the project.

Mike Gray: Coordinated the project team, funding and editing.


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Long-term cannabis use: characteristics of users in an Australian rural area

Addiction. 1998 Jun;93(6):837-46.


Northern Rivers Health Service, Lismore, New South Wales, Australia.



To investigate the characteristics and patterns of cannabis and other drug use among long-term cannabis users in an Australian rural area.


Cross-sectional survey of a "snowball" sample of long-term cannabis users.


The North Coast of New South Wales is an area with high levels of cannabis cultivation and use, and many long-term users.


The study involved 268 long-term cannabis users who had regularly used cannabis for at least 10 years.


A structured interview schedule obtained information on: demographics, social circumstances, patterns of cannabis and other drug use, contexts of use, perceptions about cannabis and legal involvement.


The mean age of the sample was 36 years and 59% were made. The median length of regular cannabis use was 19 years. Most (94%) used two or more times a week and 60% used daily, with a median of two joints per day. Two-thirds (67%) used cannabis in social settings and two-thirds grew cannabis for their own use. The most common reasons for using cannabis were for relaxation or relief of tension (61%) and enjoyment or to feel good (27%). The most commonly reported negative effects were feelings of anxiety, paranoia, or depression (21%), tiredness, lack of motivation and low energy (21%) and effects of smoke on the respiratory system (18%). The majority drank alcohol (79%) and over one-third were drinking at hazardous levels. Most were current (64%) or ex-tobacco smokers (24%). One-quarter (25%) had been charged with possession of cannabis, 11% for cultivation and 6% for supply, with non-drug offences low (8%or less). Overall, three-quarters (72%) believed that the benefits of cannabis use outweighed the risks, 21% felt there was an even balance, and 7% said cannabis had done them more harm than good.


Among long-term cannabis users in this Australian rural area, cannabis use was an integral part of everyday life and it was primarily used in social situations for the same reasons that alcohol use is used in the wider community.

[PubMed - indexed for MEDLINE]




Survey of Australians using cannabis for medical purposes

Harm Reduct J. 2005; 2: 18.
Published online 2005 October 4. doi: 10.1186/1477-7517-2-18.
PMCID: PMC1262744
Chronic Cannabis Use in the Compassionate Investigational New Drug Program:
An Examination of Benefits and Adverse Effects of Legal Clinical Cannabis (2002)

An Examination of Benefits and Adverse Effects of Legal Clinical Cannabis
Russo, E., Mathre, ML., Byrne, A., Velin, R., Bach, P., Sanchez-Ramos, J., and Kirlin, KA.

Copyright 2002 by the Haworth Press: Journal of Cannabis Therapeutics, Vol. 2(1) 2002

Presented: The Second National Clinical Conference on Cannabis Therapeutics: Analgesia and Other Indications- May 3, 2002

Summary by Jay R. Cavanaugh, Ph.D.

Most Americans are unaware that the United States Government has had a "compassionate use" Investigational New Drug (IND) program that has provided medical cannabis to patients for nearly 30 years. Only a handful of patients were ever approved to use NIDA’s University of Mississippi grown marijuana. The government cracked open the door to medical cannabis and some 15-35 patients stepped through before the door was slammed shut. Seven of these patients are still surviving and receiving their monthly allocations of medical cannabis.

Dr. Ethan Russo and co-authors express their astonishment that virtually no research has ever been conducted or published on IND program participants. Although a small sample size, these patients represent virtually the first "official" cannabis patients. They have been provided with a mediocre but consistent supply of cannabis for chronic and serious medical conditions for a period of time ranging from 11 to 27 years in the study group.

The authors approached eight surviving IND patients. One patient, the pioneer Robert Randall, died before the study was initiated. Three others chose to remain private. The four remaining patients provided informed consent and underwent an exhaustive medical review.

The two major questions that the study dealt with are:

  1. How well has cannabis worked for the conditions prescribed?
  2. What are the nature and severity of any adverse effects of long term cannabis use?

In order to answer these questions, the authors had a variety of examinations conducted with the four study participants including:

  • MRI scan of the brain
  • Pulmonary function tests (Spirometry)
  • EEG
  • Chest X-ray (two patients)
  • Endocrine assays
  • Immunological assays
  • P300 testing (EEG Memory test) (three patients)
  • Complete battery of neuropsychological tests
  • Neurological examination
  • Records review
  • Complete history

The diagnostic procedures employed were aimed at evaluating previous claims in the literature relating to alleged adverse effects including impaired immune response, abnormal hormone levels, brain damage, memory loss, etc.

The patient’s indications for adjunctive therapy with medical cannabis ranged from glaucoma to MS to Congenital Cartilaginous Exostoses to Nail-Patella Syndrome. The patients used multiple prescribed medications for their conditions along with their cannabis. The patients used approximately 7-9 grams/day of cannabis that was rated at 2.5-4.0% THC. Of major interest to AAMC and others is how this dose so closely matches that of patients in a soon to be published study of clinic patients in California. The California patients utilized 1-2 grams/day but their consistently supplied single strain is assayed at approximately 21% THC and is provided without seeds, stems, or leaf in a much fresher state than the NIDA cannabis.


Neuropsychological- "Overall, once more, no significant attributable neuropsychological sequelae are noted due to chronic cannabis usage."

Neuroimaging- "Current MRI studies on Patients A-C with a General Electric Sigma LX MR 1.5 Tesla magnet system reveal no clear abnormalities". Patient D presented MRI with the typical lesions of MS with some possible improvement over the course of cannabis therapy.

Neurophysiology- "In essence, no EEG pathology of an attributable nature seems apparent in the study group on the basis of cannabis usage."

Pulmonary- "In our patients A-C, no ultimate chest radiographic changes of significance were noted. Observed pulmonary function values in this cohort reveal no clear trends except a slight downward trend in FEV and FEV/FVC ratios." The researchers also looked at the role of low-grade NIDA cannabis as a potentially contributing factor to the modest changes in FEV and FEV/FVC. The study made a major point of addressing what the researchers called the problems with low grade, harsh medicine from NIDA.

Immunology- "All patients had CD4 counts within normal limits".

Endocrine- "None of the Patients A-D, displayed any abnormal values in any endocrine measure".

Hematological- "In our studies, Patient B, a concomitant tobacco smoker, displayed a mild degree of polycythemia and slightly elevated WBC. No other hematological changes of any type were evident in the other three patients."

Conclusions and Recommendations from paper:


1. Cannabis smoking, even of a crude, low-grade product, provides effective symptomatic relief of pain, muscle spasms, and intraocular pressure elevations in selected patients failing other modes of treatment.

2. These clinical cannabis patients are able to reduce or eliminate other prescription medicines and their accompanying side effects.

3. Clinical cannabis provides an improved quality of life in these patients.

4. The side effect profile of NIDA cannabis in chronic usage suggests some mild pulmonary risk.

5. No malignant deterioration has been observed.

6. No consistent or attributable neuropsychological or neurological deterioration has been observed.

7. No endocrine, hematological or immunological sequelae have been observed.
Russo et al. 51

8. Improvements in a clinical cannabis program would include a ready and consistent supply of sterilized, potent, organically grown unfertilized female flowering top material, thoroughly cleaned of extraneous inert fibrous matter.

9. It is the authors’ opinion that the Compassionate IND program should be reopened and extended to other patients in need of clinical cannabis.

10. Failing that, local, state and federal laws might be amended to provide regulated and monitored clinical cannabis to suitable candidates"

The bottom line of looking at patients with long term histories of serious illness and use of medical cannabis is that virtually all of the patients gained significant benefit while experiencing insignificant adverse effects other than mild lung irritation due to the poor quality of their government medication.

I was able to meet and speak with three of the four patients in this study. All are now ambulatory and functional. All are bright, attentive, and function at a high level. Dr. Russo and his co-authors have done a thorough job of documenting the experience and results of these patients with what many patients described as their "life-saving" medicine.





The morphology of the immune system in opiomania, cannabism, and polynarcotism

Zaĭrat'iants OV, Gasanov AB

Arkh Patol 2009 Sep-Oct; 71(5):35-40.

The organs of the immune system were morphologically and immunohistochemically studied in chronic opiomania (n = 219), cannabism (n = 22), and polynarcotism (n = 69) after excluding HIV-infected patients. In opiomania, immune disorders were identified in 98.6% of cases. These immune disorders differ according to their stage and characterize by the inversion of the T-helper/T-suppressor index, the reductions in the proliferative activity of lymphocytes and the production of immunoglobulins, atrophy of the thymus and T zones, and, in 37.4% of cases, persistent follicular hyperplasia of B zones with the impaired architectonics of lymphoid follicles. It is a cause of generalized lymphadenopathy and splenomegaly, which are similar to those observed in HIV infection. Infection with hepatitis B and C viruses enhances thymus and T-zone atrophy, but B-tone hyperplasia particularly in the lymph nodes of the hepatic hilum and spleen. In cannabism, the morphological signs of immunodeficiency were revealed only in 13.6% of the dead and there was no inversion of the T-helper/T-suppressor index. In polynarcotism, the involvement of immune organs is most severe and similar to that seen in opiomania.





Effects of cannabis on lung function: a population-based cohort study

Hancox RJ, Poulton R, Ely M, Welch D, Taylor DR, McLachlan CR, Greene JM, Moffitt TE, Caspi A, Sears MR 
Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
Eur Respir J 2010 Jan; 35(1):42-7.

The effects of cannabis on lung function remain unclear and may be different from those of tobacco. We compared the associations between use of these substances and lung function in a population-based cohort (n = 1,037). Cannabis and tobacco use were reported at ages 18, 21, 26 and 32 yrs.

Spirometry, plethysmography and carbon monoxide transfer factor were measured at 32 yrs. Associations between lung function and exposure to each substance were adjusted for exposure to the other substance.

Cumulative cannabis use was associated with higher forced vital capacity, total lung capacity, functional residual capacity and residual volume.

Cannabis was also associated with higher airway resistance but not with forced expiratory volume in 1 s, forced expiratory ratio or transfer factor.

These findings were similar among those who did not smoke tobacco. In contrast, tobacco use was associated with lower forced expiratory volume in 1 s, lower forced expiratory ratio, lower transfer factor and higher static lung volumes, but not with airway resistance.

Cannabis appears to have different effects on lung function from those of tobacco. Cannabis use was associated with higher lung volumes, suggesting hyperinflation and increased large-airways resistance, but there was little evidence for airflow obstruction or impairment of gas transfer.



Long-Term Marijuana Users Suffer Few Health Problems, Australian Study Indicates

NORML News, March 20, 1997

March 20, 1997, Sydney, Australia: The health of long-term marijuana users is virtually no different than that of the general population, according to the latest findings by the National Drug and Alcohol Research Centre in Australia.

The study, which involved interviews with 268 marijuana smokers and 31 non-using partners and family members, is one of the first ever conducted in Australia to determine the effects of long-term marijuana use.

Its findings were reported by the Sydney Morning Herald last month. "We don't see evidence of high psychological disturbance among the [long- term users,]" said chief investigator David Reilly. "The results seem unremarkable; the exceptional thing is that the respondents are unexceptional." Reilly did note that regular marijuana users complained of mild respiratory problems such as wheezing at about twice the rate of non- users. He warned that this result may be because nearly all of the marijuana users were also current or former tobacco smokers. "The greatest danger to health posed by marijuana is prohibition," stated NORML's Deputy Director Allen St. Pierre.

The findings of the Australian study echo statements made approximately one-year ago by the premiere British medical journal, The Lancet, which proclaimed, "The smoking of cannabis, even long term, is not harmful to health." The Lancet article further went on to recommend decriminalizing marijuana.

For more information, please contact either Allen St. Pierre of NORML @ (202) 483-5500 or Jamnes Danenberg of HEMP SA of Australia @ (+61) 8 297-9442 or via e-mail at: