effects of medical marijuana based on strain and route of administration: A three-year
Alliance for Medical Marijuana
Cedar Street #39
Cruz, CA 95060
collective of patients and caregivers, creating community, building hope, dissolving
barriers, providing support and free medical marijuana since 1993
displays substantial effectiveness to affect a variety of medical symptoms. Seventy-seven
patients took part in a study in California to assess the efficacy of organically
grown Cannabis sativa and indica strains in treatment of various medical conditions
via smoking or ingestion. HIV/AIDS was the most frequent condition reported, at
51%. Standardized rating forms provided 1892 records that were statistically analyzed.
Results demonstrated that in the case of nausea and spasm, changes in symptom
expression are definitely affected by method of cannabis administration. However,
while Cannabis indica strains increased energy and appetite, it is useful to note
that in treating nausea in HIV/AIDS and orthopedic diagnosis groups, Cannabis
sativa and C. indica strains proved equivalent.
Keywords: cannabis, medical
marijuana, Cannabis sativa, Cannabis indica, AIDS, HIV
Marijuana, whether Cannabis sativa and Cannabis indica, produces
its medical and other effects by virtue of the concentration and balance of various
active ingredients, especially the cannabinoids, which are unique to marijuana,
but including also a wide range of terpenoids and flavonoids (McPartland and Mediavilla
2001; McPartland and Pruitt 1999). Terpenoids are cannabis constituents that provide
the characteristic strong odor of marijuana and hashish. Flavonoids are any of
the flavone derivatives. The concentration and relative proportions of these ingredients
depend on the plant's genetic structure and applied hybridization techniques,
and as such, allow for a substantially varied outcome.
is known about how differences in constituent profiles translate into differences
in therapeutic effectiveness. A range of differentiable effects has been ascribed
to THC (tetrahydrocannabinol is the primary psychoactive component of marijuana)
and CBD (cannabidiol, a compound related to THC) when administered in purified
form (Iversen 2000). Studies are lacking on the differential clinical effects
produced when varying "menus" of constituents are taken together.
factor bearing on the effects and the effectiveness of marijuana is the route
of administration. Orally administered marijuana is absorbed more slowly than
when delivered systemically (e.g., smoking, vaporizers). Moreover, the liver metabolizes
orally ingested marijuana. This produces a potent and long-acting cannabinoid
(11-hydroxy-THC), which induces varied reactions in medical marijuana patients
and is not often well tolerated (Grotenhermen 2001). However, once more, there
is little information available concerning the differential clinical effects of
oral vs. smoked forms of marijuana.
major obstacle to obtaining data concerning differential clinical effects produced
by varying strains of cannabis and by different routes of administration is, of
course, the common illegality of medical marijuana use. Almost equally troublesome,
however, is the widespread view that medical knowledge can be gained only through
randomized controlled trials. It is becoming increasingly accepted that valid
causal inferences can be, and frequently are drawn quite regularly in medicine
without such studies. As such, observational studies are quite capable of generating
useful information, provided due care is taken to keep careful track of the process.
In this case, careful and consistent documentation would be required concerning:
1) which forms of marijuana are being taken, by what route, and: 2) what outcome
is experienced by patients.
passage of Proposition 215 in California in 1996 legalized medical marijuana under
state law, thus clearing some legal obstacles to research. Prior to the passage
of Proposition 215, two or more cannabis buyers’ clubs and our collective
comprised of patients and caregivers were in operation. Several provider associations
have been operating since that time despite harassment of some by law enforcement
Leveroni Corral founded the Wo/Men’s Alliance for Medical Marijuana, WAMM
in 1993. WAMM is a collective of patients and caregivers attempting to create
community, build hope, dissolve barriers, and provide support and medical marijuana
at no cost to patient members who possess a signed and verified recommendation
from a physician licensed to practice medicine in California. A genetically monitored,
organic, communal garden is tended by WAMM client/ participants under the direction
of Mike Corral and Valerie A. Leveroni Corral.
primary function in this community based educational system is the creation of
a database of information regarding the treatment of different symptoms with distinct
cannabis varieties. This is achieved through daily effectiveness surveys and statistical
analysis. Our present collection of data also includes measures of effectiveness
of cannabis on other autoimmune illnesses, such as systemic lupus erythematosis,
as well the many other disorders, including muscular dystrophy, epilepsy, quadriplegia,
paraplegia, Parkinson's disease, glaucoma, arthritis, fibromyalgia, depression
and migraine. However, AIDS and HIV-related conditions are the most frequently
represented among our clientele.
initiated a study in 1993 designed to address the question of differential clinical
effects between Cannabis sativa and C. indica strains and hybrids, and also examining
effects of inhaled and ingested routes of administration. This study is ongoing
and now includes "blind" trials where the varieties used are not apparent
to the participating patient. A statistician determined all analyses. [Tables
17 & 18]
Materials and Methods
of the variety of cannabis was based on the country of origin of the seeds strains
and physical characteristics of each plant variety. We assure the genetic purity
through carefully controlled breeding techniques, substantiated by twenty-five
years of experience in cultivation, propagation and breeding of cannabis. Personal
interaction took place with patient use of cannabis in more than one hundred different
assessment instrument form is provided weekly to participating patients [see Tables
17 & 18]. The patient places a label from a weekly supply on the seven day
form, denoting the variety and form of cannabis (inhaled or ingested), the number
of "puffs" if inhaled medicine is used and the amount or weight employed.
All participants were instructed in a specific method for inhaling. Patients were
requested to use and denote dosages correlated to the relief of specific symptomatology.
Participants observed and rated symptoms before and after cannabis use to record
their severity. This is done upon rising from sleep in all cases except "insomnia"
and prior to using any cannabis. Assessments were made weekly, at minimum, or
as much as seven times per week, in order to assess effectiveness and of different
strains upon different target symptoms.
were derived from data gathered during the time period of June of 1993 into early
1997. Statistical analysis consisted of frequency analysis, paired T-tests of
"before" and "after" scores on each measured symptom or condition,
and a series of one way ANOVAs on route of administration (either inhaled or ingested,
cannabis strain, and diagnosis).
the therapeutic effects of cannabis are sometimes ascribed to its mood-altering
effects, we also performed a correlation analysis of the change in mood score
with other outcome variables.
methods of cannabis consisted mostly of smoking, with some use of vaporization,
although patient reports of effectiveness appear substantially lessened when this
technique was employed. This could certainly depend on the quality of the vaporizer
forms of cannabis consisted of baked goods and "mother's milk" (a soymilk-based
liquid), and a whole cannabis tincture made with pure grain alcohol with leaf
or a combined blend of leaf and flowers. Strains of marijuana were C. sativa and
C. indica and their hybrids. The morphological distinction between these strains
was determined by experienced cannabis cultivators associated with WAMM, based
on characteristic features of the two sub-species, varieties or strains.
sub-species varied from week to week and included the following pure strains and
sativa, C. indica, as well as hybrids of both, being the identified female C.
sativa x male C. indica, as well as the identified female C. indica x male C.
sativa. We secured a method of analysis of the chemical content of test materials,
although we believe that the findings may be subject to error. Results from a
drug detection laboratory indicated that C. sativa measured: THC 23.7%, CBD <0.1%
and CBN <0.1%. Results indicated that C. indica strains measured THC 19.6%,
CBD <0.2% and CBN <0.5%. Cannabis potency testing results by ElSohly Labs
of the same sample of C. sativa after storage for eight months yielded a value
of THC 17.6 %.
completed a total of 1892 forms (range 1 - 256, median 8) during the three-year
study period. Of these, 43 were male (56 percent), 22 were female (29 percent)
and 12 were not coded as to gender. The distribution of primary diagnosis is presented
in Table 1. [Table 1]
patients (51 percent) had HIV/AIDS; 14 (18 percent) had neurological diseases,
and 7 (9 percent) had a principle diagnosis of cancer.
avoid biasing results due to a large proportion of questionnaires being completed
by relatively few patients, we standardized the analysis by reviewing a maximum
of eight records per patient, the median number completed by study subjects. These
records were randomly chosen. Accordingly, our analysis contained 432 records.
Of these, 261 (61 percent) referred to C. sativa experiences; 65 (15 percent)
were C. indica, while 105 (24 percent) were coded "other". Certain types
of marijuana were donated or undeclared, we labeled these as "other"
and included them in our findings. Ingested forms were also recorded [Table 4].
Some entries were coded with missing information, entered as slang or incorrectly
named, these were excluded.
t-tests of before and after health status revealed that the following symptoms
were relieved to a statistically significant extent by marijuana (without regard
to strain or route of administration): pain, energy, mood, nausea, appetite, and
awareness. The remaining symptoms were not reliably relieved to this extent. Table
5 and Table 6 show the scores on each variable. The magnitude of improvement was
unrelated to clinical diagnosis, as determined in ANOVA [Table 10], with one exception:
the degree of relief of nausea was greater in the HIV/AIDS group (4.54 units)
than in the orthopedic group (1.58 units) to a (marginally) statistically significant
extent (p = 0.04).
next performed ANOVA on the strain of marijuana ingested: C. sativa and C. indica.
The mean change scores, "before" scores minus "after" scores
for patients with each condition. For the most part, some observed changes were
unrelated to strain of marijuana. However, two symptoms - energy and appetite
- were improved to a statistically greater extent by C. indica than by either
C. sativa or "other."
indica produced a mean improvement in energy of 3.76 units (vs. 1.53 for C. sativa
and 2.22 for "other") and a mean improvement in appetite by 5.22 units
(vs. 3.41 for C. sativa and 4.32 for C. indica). These differences were significant
at the 0.012 and 0.005 levels, respectively [Table 8].
was then conducted using route of administration as the independent variable [Table
6 & Table 7]. For the most part, ingested and inhaled marijuana had similar
magnitudes of effects. Only one symptom - spasm - showed preferential improvement
using smoked over ingested marijuana (p = .036). [Table 6]. Patients reporting
"other" routes of administration, such as ingestion, had substantially
less relief of nausea than patients inhaling or ingesting marijuana [Table 7].
is reported that THC may reduce spasms associated with both neurological and non-neurological
disorders (Hollister, 1986; British Medical Association Report, 1997). It is interesting
to note that the non-psychoactive cannabinoid cannabidiol has been shown to exhibit
anticonvulsant properties in certain animal studies (Iversen 2000)(The Science
of Marijuana, L.L. Iversen, Ph D.) In the case of some patients it has been noted
to reduce or prevent the onset of both spasms and seizures when used alone or
as an adjunct medicine. It appears that there are receptor sites for cannabinoids
that have beneficial effects on seizure activity.
analysis of the Pearson correlation coefficients between changes in mood scores
and changes in other symptom scores revealed only a single statistically significant
correlation, between mood and energy level (p = 0.035). Mood was not correlated
with any other outcomes, including pain relief (p = 0.817) [Table 11].
We analyzed 432 records of therapeutic cannabis
exposures, including information on strain (C. sativa, C. indica, or other), and
route of administration (inhaled, ingested or other). The outcome variables consisted
of scores to a series of questions on symptoms, completed by the patient both
before and after administering cannabis medicines.
indicate that cannabis was uniformly effective in relieving symptoms across a
wide range of diagnostic categories. No differences were observed in the extent
to which symptoms were relieved based on diagnosis, except that patients with
HIV/AIDS experienced more relief of nausea than patients with primary orthopedic
diagnoses [Table 13].
several occasions, terminally ill patients remarked upon a recurrent phenomenon,
described as a “shift in consciousness" or "perception" allowing
them to approach their impending death more "openly" or in a more "relaxed"
manner. This is of particular interest, as each patient also reported a reduction
in anxiety often associated with the dying process. Future studies will further
examine measures anxiety in the cannabis patient population.
indica appeared to be superior to C. sativa and "other" in improving
energy and appetite [Table 9]; otherwise, no differences in strain effects were
observed. Route of administration had little effect on outcome in our series.
Two symptoms, spasm [Table 6] and nausea [Table 7] showed preferential improvement
of smoking as compared ingestion. In no condition was the ingested route superior
to smoking upon symptom management.
in mood were not correlated with changes in other outcomes except for a modest
correlation with energy [Table 11]. The finding that mood did not correlate with
other outcomes casts doubt on the theory that therapeutic cannabis effects are
related primarily to improvement in mood. Conversely, this may have something
to do with the notion suggested by some patients that mood is not necessarily
correlated to the concept of "feeling better." In our findings, it appeared
that mood was often independent of symptom expression. This result is interesting
because it appears from written testimony by patients in their surveys that they
believe changes in awareness or consciousness do affect overall healing. We plan
to further examine the validity of these phenomena in future studies.
findings support that few differences were noted by patients between C. sativa
and C. indica strains and between ingestion vs. inhaled routes of administration.
This is likely due to modest observed differences in cannabinoid content in the
supplied strains. We hope that a reliable and accessible means of analysis will
become available in the near future.
study is limited by the lack of blinding. For this reason, in 1998 a revised protocol
was instituted in which patients receive a one-week supply of therapeutic cannabis
at a time without knowledge of particular variety provided. Patients continue
completing forms on a weekly basis. This method of blinding is expected to provide
a more rigorous test of any distinctions between C. sativa and C. indica strains.
Results may have implications for subsequent crossbreeding of strains to maximize
study is only a small first step in the attempt to develop improved cannabis medicines
to affected patients. The most significant current limitation to this type of
research is the absence of a convenient legal mechanism in the USA for analyzing
cannabis samples for biochemical constituent content. Until this limitation is
overcome, progress in this area will be slow at best.
the other hand, we should not underestimate the value of clinical observation
in judging strains of cannabis and their differential clinical effects irrespective
of chemical content. Thus, while the work we report here does not definitely address
issues of chemical variability, we believe that our findings provide at the very
least a good working hypotheses for use in future studies.
Grotenhermen, Franjo. 2001. Practical hints. In Cannabis and
Cannabinoids: Pharmacology, toxicology and therapeutic potential, edited by F.
Grotenhermen and E. Russo. Binghamton, NY: Haworth Press.
Leslie L. 2000. The science of marijuana. Oxford ; New York: Oxford University
J. M., and P. L. Pruitt. 1999. Side effects of pharmaceuticals not elicited by
comparable herbal medicines: the case of tetrahydrocannabinol and marijuana. Altern
Ther Health Med 5 (4):57-62.
John M., and Vito Mediavilla. 2001. Non-cannabinoids in cannabis. In Cannabis
and cannabinoids, edited by F. Grotenhermen and E. B. Russo. Binghamton, NY: Haworth
September 21, 2000
in Final Form: April 29, 2001.
of the Project
determine if there are physical, mood and perception changes resulting from use
of the test article.
To determine if the method of delivery affects measures of effectiveness.
To determine if different types of cannabis affect diagnoses and measures of effectiveness.
To assess the correlation between changes in mood and other measures of effectiveness.
Summary of Population
N = 77
missing gender distinction (15%)
of Population by Primary Diagnosis
of Patient Population by Secondary Diagnosis
Structure Measures of Effectiveness
1892 Questionnaires Completed over 3 years
Range of 1 to 256 questionnaires
Average of 8 questionnaires/patient
Analysis completed based on the average number of questionnaires completed (to
normalize data for analysis)
432 questionnaires analyzed
Frequency analysis, Paired t-tests, Paired t-test correlations, One Way ANOVA,
Post-Hoc (Bonferroni), Pearson Correlation and Multivariate tests performed
One Way ANOVA conducted on variables using the following 3 groups
1 – test article “ingested”
2 – test article “inhaled”
One Way ANOVA performed on the following test article groups:
(261 – 61%)
(105 – 24%)
( 65 – 15%)
Multivariate Tests performed for type of Cannabis, diagnosis, and change in variable
of Between-Subjects Effects
One Way ANOVA, Bonferroni, Post-Hoc tests performed for definition of diagnosis
and treatment effectiveness
tests performed using SPSS (Statistical Program for Social Scientists) Version
Are there physical, mood and perception changes resulting from use of
the test article?
Paired Samples t test
Comparing means before and after
confidence interval (2-tailed)
Does change in variable vary by method of treatment - ingested, inhaled
Question Two - Means of Variable Changes by Mode of Consumption
Examination of the mean change (One way Anova –
95% confidence interval)
was found for the following variables
p = 0.008
p = 0.036
of ANOVA Method of Test Article Delivery
Group 1 is different than group 3
Average group 1 (ingested) = -4.39
Average group 2 (inhaled) = -4.50
Average group 3 (other) = -2.20
There is greater improvement in nausea (0.36) with ingestables vs. “other”
Ingestables and inhaled groups are not different
Are changes in variables related to the different types of cannabis
and primary diagnoses?
Change of Variables in Treatment Test Article Groups
Way Anova – 95% CI
Interpretation of ANOVA Method of Test Article Treatment
The Indica Group is different than Sativa Group
Indica = 3.06
Sativa = 1.53
Other = 2.22
There is greater improvement in energy (0.012) with Indica vs Sativa and “Other”
Sativa and Other treatment groups are not different
of ANOVA Treatment Group
Indica was more effective to increase energy and appetite in any primary diagnosis
Use of any test article was effective in treating Nausea in the Orthopedic and
HIV/AIDS diagnosis group.
Change in Variable by Primary Diagnosis
Way Anova 95% CI
**Small sample size unable to correlate
of ANOVA Method for Primary Diagnostic Group
The Orthopedic and Neurologic group are different than the “Other”
primary diagnostic group.
There is greater improvement in Mood (p = 0.008) for the Orthopedic group vs.
There is greater improvement in Mood (p = 0.001) for the Neurologic group vs.
is no difference between the AID/HIV and Cancer groups
Interpretation of ANOVA Method for Primary Diagnostic Group
The Orthopedic group is different than the “Other” primary diagnostic
There is greater improvement in Energy (p = 0.43) for the Orthopedic group than
is no difference between the Neurologic, AID/HIV, and Cancer groups
Interpretation of ANOVA Method for Primary Diagnostic Group
The HIV/AIDS group is different than the Orthopedic primary diagnostic group
There is greater improvement in Nausea (p =0.04) in the HIV/AIDS group than Orthopedic
primary diagnostic group
is no difference between the Neurologic, Other, and Cancer groups
of ANOVA Method for Primary Diagnostic Group
There is improvement in Appetite (0.010) for all diagnostic groups
There is no difference in mean change for the Appetite variable for specific primary
of ANOVA Method for Primary Diagnostic Group
There is improvement in Insomnia (p = 0.000) for all diagnostic groups
is no difference in mean change for the Insomnia variable for specific primary
of ANOVA Method for Primary Diagnostic Group
There is improvement in Awareness (p = 0.000) for all diagnostic groups
There is no difference in mean change for Awareness specific to primary diagnostic
Analysis Question Four
Is change in mood correlated to change in energy?
Is change in mood correlated to change in pain?
Is change in mood correlated to change in nausea?
Is change in mood correlated to change in insomnia?
Is change in mood correlated to change in awareness?
There were observed changes in pain, energy, nausea, appetite, and awareness variables
from the use of the test article.