Valerie Leveroni Corral
Wo/Men's
Alliance for Medical Marijuana
309 Cedar Street
#39
Santa Cruz, CA 95060
A collective of patients and caregivers,
creating community, building hope,
dissolving barriers, providing support
and free medical marijuana since 1993
Quick
Links:
Introduction
| Materials and Methods | Results
| Discussion | References
| Purpose of Project | Summary of
Population | tables | Conclusions
Abstract
Cannabis 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. Little 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. Another
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. A 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. The 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 agencies. Valerie
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. A 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. WAMM 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 |
The
determination 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 terminal cases. An 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. Findings 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). Because 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. Inhalation
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 design. Ingested
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. These
sub-species varied from week to week and included the following pure
strains and hybrid strains: C. 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 %. |
Seventy-seven
patients 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] Thirty-nine
patients (51 percent) had HIV/AIDS; 14 (18 percent) had neurological
diseases, and 7 (9 percent) had a principle diagnosis of cancer. To 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. Paired
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). We 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." C. 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]. ANOVA 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]. It 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. Finally,
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. Results
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]. On 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. C. 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. Changes 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. These
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. This 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 therapeutic effects.
This 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. On 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. Iversen, Leslie L. 2000. The science of marijuana. Oxford ; New York: Oxford University Press. McPartland, 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. McPartland, 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 Press. |
Received: September 21, 2000
Accepted in Final Form: April 29, 2001.
N = 77
43 males (56%)
22 females (29%)
12 missing gender distinction (15%)
Table
1
Description
of Population by Primary Diagnosis
Table
2
Description
of Patient Population by Secondary Diagnosis
Table 3
Questionnaire Structure Measures of Effectiveness
Variable |
None |
Most |
Desired Effect |
Pain |
1 |
10 |
Decrease |
Energy |
1 |
10 |
Increase |
Mood |
1 |
10 |
Increase |
Nausea |
1 |
10 |
Decrease |
Appetite |
1 |
10 |
Increase |
Muscle Spasms |
1 |
10 |
Decrease |
Seizures |
1 |
10 |
Decrease |
Ocular |
1 |
10 |
Decrease |
Insomnia |
1 |
10 |
Decrease |
Awareness |
1 |
10 |
Increase |
Neuropathy |
1 |
10 |
Decrease |
Table 4
�
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
Group
1 � test article �ingested�
Muffins
Mothers
milk
Group
2 � test article �inhaled�
African
Queen
Purple
Indica
Group
3 ��Other�
� One Way ANOVA performed on the following test article groups:
Sativa
(261 � 61%)
Other
(105 � 24%)
Indica
(
65 � 15%)
� Multivariate Tests performed for type of Cannabis, diagnosis, and change in variable
Pillai�s
Trace
Wilks�
Lambda, and
Tests
of Between-Subjects Effects
� One Way ANOVA, Bonferroni, Post-Hoc tests performed for definition of diagnosis and treatment effectiveness
All tests performed using SPSS (Statistical Program for Social Scientists) Version 9.0
�
Are
there physical, mood and perception changes resulting from use of the test
article?
�
Comparing
means before and after
95%
confidence interval (2-tailed)
Variable |
Before |
After |
Difference |
Pain |
6.98 |
3.26 |
-3.72
+/- 3 |
Energy |
4.12 |
6.04 |
1.92
+/- 3 |
Mood |
4.30 |
7.32 |
3.02
+/- 4 |
Nausea |
7.06 |
2.78 |
-4.28
+/- 3 |
Appetite |
3.02 |
6.96 |
3.94
+/- 4 |
Awareness |
5.73 |
6.97 |
1.24
+/- 3 |
All
are significant
�
Does
change in variable vary by method of treatment - ingested, inhaled or other?
|
1 |
2 |
3 |
P |
Pain |
-3.75 |
-3.45 |
-3.67 |
0.274 |
Energy |
2.05 |
1.14 |
1.18 |
0.630 |
Mood |
2.98 |
2.54 |
3.81 |
0.840 |
Nausea |
-4.39 |
-4.50 |
-2.22 |
0.934 |
Appetite |
4.05 |
2.94 |
3.28 |
0.418 |
Spasm |
-3.42 |
-3.95 |
-3.60 |
0.008* |
Seizure |
-0.14 |
N/A |
-4.75 |
0.117 |
Ocular |
-2.63 |
-2.54 |
-2.86 |
0.099 |
Insomnia |
-3.88 |
-3.44 |
-4.28 |
0.036* |
Awareness |
1.31 |
-0.41 |
1.72 |
0.259 |
*Significant
Examination
of the mean change (One way Anova � 95% confidence interval)
Significance
was found for the following variables
Spasm
p = 0.008
Table
7
�
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?
Table
8
|
Other |
Sativa |
Indica |
P |
Pain |
-3.49 |
-3.99 |
-2.93 |
0.078 |
Energy |
2.22 |
1.53 |
3.06 |
0.012* |
Mood |
2.94 |
2.89 |
3.76 |
0.327 |
Nausea |
-4.67 |
-4.19 |
-4.01 |
0.470 |
Appetite |
4.32 |
3.41 |
5.22 |
0.005* |
Spasm |
-4.33 |
-3.53 |
-2.23 |
0.071 |
Seizure |
-0.67 |
-2.12 |
0.50 |
0.316 |
Ocular |
-3.27 |
-2.34 |
-3.00 |
0.646 |
Insomnia |
-4.53 |
-3.82 |
-3.18 |
0.221 |
Awareness |
1.75 |
0.96 |
1.24 |
0.173 |
One
Way Anova � 95% CI
*Significant
�
The
Indica Group is different than Sativa Group
Average
Indica = 3.06
Average
Sativa = 1.53
Average
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
�
Indica
was more effective to increase energy and appetite in any primary diagnosis
group.
�
Use
of any test article was effective in treating Nausea in the Orthopedic and
HIV/AIDS diagnosis group.
Table
10
|
Ortho |
Neuro |
AIDS |
Other |
Cancer |
P |
Mood |
4.36 |
4.05 |
2.87 |
1.33 |
2.64 |
0.001* |
Pain |
-4.93 |
-4.02 |
-3.31 |
-3.90 |
-3.27 |
0.011* |
Energy |
3.54 |
1.33 |
2.31 |
1.07 |
1.23 |
0.017* |
Mood |
4.36 |
4.05 |
2.86 |
1.33 |
2.64 |
0.094 |
Nausea |
-1.58 |
-4.21 |
-4.54 |
-3.97 |
-4.18 |
0.015* |
Appetite |
4.57 |
3.50 |
4.44 |
3.08 |
3.00 |
0.010* |
Spasm |
-4.17 |
-4.05 |
-1.83 |
-3.29 |
-4.91 |
0.401 |
Seizures |
NA |
-1.86 |
-0.89 |
NA |
NA |
0.001** |
Ocular |
NA |
-2.91 |
-2.00 |
-4.00 |
NA |
0.334 |
Insomnia |
-4.68 |
-4.66 |
-3.49 |
-2.93 |
-5.08 |
0.000* |
Awareness |
2.21 |
1.07 |
1.15 |
0.65 |
2.25 |
0.000* |
One
Way Anova 95% CI
*Significant
**Small sample size unable to correlate
Table
11
�
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.
�Other�
�
There
is greater improvement in Mood (p = 0.001) for the Neurologic group vs.
�Other�
Average
Orthopedic
4.36
Average
Neurologic
4.04
Average
HIV/AIDS
2.87
Average
�Other�
1.33
Average
Cancer
2.64
� There is no difference between the AID/HIV and Cancer groups
�
The
Orthopedic group is different than the �Other� primary diagnostic group.
�
There
is greater improvement in Energy (p = 0.43) for the Orthopedic group than
�Other�
Average
Orthopedic
3.54
Average
Neurologic
1.33
Average
HIV/AIDS
2.31
Average
�Other�
1.07
Average
Cancer
1.23
�
There
is no difference between the Neurologic, AID/HIV, and Cancer groups
�
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
Average
Orthopedic
-1.58
Average
Neurologic
-4.21
Average
HIV/AIDS
-4.54
Average
�Other�
-3.97
Average
Cancer
-4.18
�
There is no difference between the Neurologic, Other, and Cancer
groups
Table
14
�
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
diagnostic groups
Average
Orthopedic
4.57
Average
Neurologic
3.50
Average
HIV/AIDS
4.44
Average
�Other�
3.08
Average
Cancer
3.00
Table
15
�
There
is improvement in Insomnia (p = 0.000) for all diagnostic groups
There is no difference in mean change for the Insomnia variable for specific primary diagnostic groups
Average
Orthopedic
-4.68
Average
Neurologic
-4.66
Average
HIV/AIDS
-3.49
Average
�Other�
-2.93
Average
Cancer
-5.08
Table
16
�
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
groups
Average
Orthopedic
2.21
Average
Neurologic
1.07
Average
HIV/AIDS
1.15
Average
�Other�
0.65
Average
Cancer
2.25
�
Is
change in mood correlated to change in energy?
p
= .035*
�
Is
change in mood correlated to change in pain?
p
= .817
�
Is
change in mood correlated to change in nausea?
p
= .434
�
Is
change in mood correlated to change in insomnia?
P
= .647
�
Is
change in mood correlated to change in awareness?
P
= .073
*Significant
�
There
were observed changes in pain, energy, nausea, appetite, and awareness
variables from the use of the test article.
Introduction
| Materials and Methods | Results
| Discussion | References
| Purpose of Project | Summary of
Population | tables | Conclusions