In uno studio
clinico condotto al San Francisco General Hospital su 50 pazienti con HIV,
sofferenti di dolore neuropatico, la cannabis fumata ha determinato una
significativa riduzione del dolore in confronto al placebo. I pazienti sono
stati randomizzati in due gruppi, che fumavano cannabis (al 3.56 per
cento di THC, quindi con dose di circa 25 mg di THC) o identiche sigarette
placebo senza cannabinoidi, tre volte al giorno per 5 giorni. Tutti i
partecipanti avevano esperienza di uso di cannabis. 31 usavano altri farmaci
contro il dolore, tra cui oppioidi e gabapentin, e continuarono a usarli per
tutto lo studio a dosi stabili.
La Cannabis
ridusse il dolore quotidiano del 34 per cento (riduzione mediana) rispetto al
17 per cento del placebo. Una riduzione del dolre maggiore del 30 per cento è
stata riferita dal 52 per cento nel gruppo che aveva ricevuto cannabis e dal 24
per cento nel gruppo che aveva ricevuto placebo. La Cannabis ridusse
il dolore anche in due tipi di dolore sperimentalmente indotto, mentre fu inefficace
in un terzo tipo. Gli effetti collaterali sono stati più comuni nel gruppo
trattato con cannabis. Non sono state riportate reazioni avverse gravi e nessun
paziente di è ritirato dallo studio a causa degli effetti collaterali. I
ricercatori conclufdono che "la cannabis è stata ben tollerata e ha
alleviato efficacemente il dolore neuropatico cronico da neuropatia sensoriale
associata a HIV. I risultati sono confrontabili con quelli dei farmaci orali
usati per il dolore neuropatico cronico”.
Il dolore
neuropatico deriva da danni ai nervi. In questo studio il dolore deriva
dall’infezione HIV infection, dai farmaci usati per trattarla o da entrambi.
L’abstract dello
studio è disponibile su: http://www.cannabismed.org/studies/study.php
(Fonte: Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL. Cannabis in painful HIVassociated sensory neuropathy: A randomized placebocontrolled trial. Neurology 2007;68(7):51521.)
Uno studio
clinico condotto dal San Francisco General Hospital in 50 pazienti
sieropositivi affetti da dolore neuropatico ha dimostrato l'efficacia della
cannabis fumata, raffrontata al placebo, nel miglioramento dei sintomi. I
pazienti coinvolti nello studio erano tutti affetti da dolore neuropatico,
causato dal virus HIV, dai farmaci antivirali o da entrambi. I pazienti sono
stati assegnati casualmente a due gruppi di trattamento. Il primo gruppo veniva
addestrato ad assumere cannabis per via inalatoria (contenente THC al 3.56 % ,
circa 25 mg di principio attivo) tre volte al giorno, mentre al secondo gruppo
veniva somministrato, sempre per via inalatoria, un placebo. I pazienti già in
terapia antidolorifica "convenzionale" continuavano ad assumere
regolarmente i farmaci abituali. Secondo quanto riportato dai ricercatori
californiani, guidati dal Dott. Donald Abrams, la assunzione di Cannabis
risultò associata ad una riduzione media del 34% del dolore contro il 17% del
placebo. Nel 52% dei pazienti che assumevano cannabis la riduzione del dolore
risultò essere maggiore del 30% contro il 24% del gruppo placebo. Il gruppo di
pazienti trattati con cannabis mostrava una maggiore incidenza di effetti
collaterali ma in nessun caso la entità di tali effetti è risultata tale da
obbligare alla sospensione della terapia. I ricercatori concludono asserendo
che "la cannabis è stata nel complesso ben tollerata ed efficace nel
mitigare il dolore neuropatico cronico associate all'HIV." Fonte:
Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC,
Petersen KL. Cannabis in painful HIV-associated sensory neuropathy: A
randomized placebo-controlled trial. Neurology 2007;68(7):515-21.) L'abstract dello studio è disponibile su:
http://www.cannabis-med.org/studies/study.php
Ricercatori
della Columbia University di New York hanno studiato gli effetti del THC orale
(10, 20 e 30 mg) e di sigarette di cannabis a diverso contenuto di THC (1,8%,
2,8% e 3,9%) sulla assunzione di cibo, in otto sessioni di 7 ore ciascuna in
due gruppi di fumatori di cannabis HIV positivi. Un gruppo era formato da 15
soggetti con una significativa riduzione della massa muscolare e l’altro da 15
soggetti senza perdita di massa magra.
Il fumo
di sigaretta (a tutte le concentrazioni di THC) e le due dosi più basse (10 e
20 mg) di THC sono risultate efficaci e ben tollerate con sintomi fisici molto
ridotti. Al contrario, la dose più alta di THC ha provocato effetti collaterali
importanti in alcuni dei partecipanti allo studio. Sia il THC orale che il fumo
di cannabis hanno determinato un maggiore introito calorico nel gruppo con
perdita di peso ma non in quello di riferimento. Gli effetti cognitivi sono
stati minimi.
Gli
autori concludono che “in soggetti fumatori di marijuana con una perdita di
massa muscolare clinicamente rilevante sia il dronabinolo (in dosi acute da 4 a
8 volte superiori rispetto a quelle consigliate) sia la marijuana inducono un
evidente e simile aumento dell’assunzione di cibo, senza effetti indesiderati.
(Fonte
: Haney M. et al. Dronabinol and
marijuana in HIV+ marijuana smokers: acute effects on caloric intake and mood. Psychopharmacology
2005, 19 Marzo; [Pubblicazione elettronica anticipata]).
Cannabis Therapeutics in HIV/AIDS
Journal of Cannabis Therapeutics Volume 1, Numbers 3/4
CONTENTS
Introduction: Cannabis
Therapeutics in HIV/AIDS, Plus, a Modest Proposal 1
Ethan Russo
Therapeutic Cannabis
(Marijuana) as an Antiemetic and Appetite Stimulant in Persons with Acquired
Immunodeficiency Syndrome (AIDS) 5
Richard E. Bayer
Acquired immunodeficiency
syndrome (AIDS) is a common cause of death among young adults in the USA. AIDS
wasting syndrome is the most common clinical presentation of AIDS.
Antiretroviral drug therapy has improved the prognosis of persons with AIDS,
but also contributed side effects, particularly nausea and anorexia. Case
reports demonstrate persons with AIDS use cannabis as medicine to control
nausea, anorexia, and pain, while noting improved mood. Recent clinical
research comparing smoked cannabis to oral dronabinol (synthetic THC or Marinolâ) demonstrates no immune dysfunction
in persons using cannabinoids and positive weight gain when cannabinoids are
compared to placebo. Harm reduction research indicates that heating cannabis to
temperatures well below combustion ("vaporization") yields active
cannabinoids and a significant reduction or elimination of toxics (benzene,
toluene, naphthalene, carbon monoxide, and tars) commonly found in smoked
cannabis. More research is indicated but vaporizers appear to substantially
reduce what is widely perceived as the leading health risk of cannabis, namely
respiratory damage from smoking. In spite of a need for more rigorous
scientifically controlled research, an increasing number of persons with AIDS
are using cannabis to control nausea, increase appetite, promote weight gain,
decrease pain, and improve mood.
KEYWORDS. Cannabis,
marijuana, dronabinol, THC, Marinolâ, AIDS, HIV, harm reduction,
immunodeficiency, vaporization, vaporizer, wasting, anorexia, nausea, appetite,
pain
Medical Marijuana and the
AIDS Crisis 17
Clinton A. Werner
The sudden emergence of the
AIDS epidemic and the initial lack of effective treatments politicized the
patient population into demanding quicker development of and access to
promising medications. When numerous AIDS patients demanded marijuana to treat
the anorexia and wasting syndrome resulting from both illness and medications,
the federal government’s Public Health Service closed the only legal source of
supply. The federal authorities’ abdication of compassion and repression of
research spawned a grassroots political movement that repudiated federal
regulations.
KEYWORDS. Acquired Immune
Deficiency Syndrome (AIDS), HIV, cannabis, marijuana, medical marijuana,
delta-9-tetrahydrocannabinol, AIDS-wasting syndrome, azidothymidine (AZT),
dronabinol
Marijuana Use in
HIV-Positive and AIDS Patients: Results of an Anonymous Mail Survey 35
Stephen Sidney
While there is a great deal
of anecdotal reporting regarding the medical use of marijuana in HIV-positive
patients, there have been few systematic surveys performed. The prevalence of
medical use of marijuana in HIV-positive and AIDS patients was assessed by an
anonymous mail survey of 1970 attendees of HIV clinics in the San Francisco,
Oakland, and South Sacramento medical centers of the Kaiser Permanente Medical
Care Program (KPMCP) in California. Of 442 responders (22.4% response rate),
147 (33.3%) reported current use of marijuana for medical purposes. Among
current users, the most common reasons for using cannabis were: to feel better
mentally/reduce stress (79%), improve appetite/gain weight (67%) and decrease
nausea (66%). Patterns of use were heterogeneous, with daily use of cannabis
reported by 34% of current users. Nearly half of participants reported buyers’
clubs as a source for obtaining cannabis, a finding of particular interest
because of recent successful government efforts in closing down these clubs in
California. In combination with other reported surveys, these data suggest that
the use of marijuana for medical purposes is relatively common in HIV-positive
and AIDS patients.
KEYWORDS. Marijuana,
cannabis, HIV, AIDS, epidemiology
Differential Effects of
Medical Marijuana Based on Strain and Route of Administration: A Three-Year
Observational Study 43
Valerie Leveroni Corral
Cannabis displays
substantial effectiveness for 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, symptom expressions are definitely affected by various
methods 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 and Cannabinoids:
Effects on Infections, Immunity, and AIDS 61
Guy A. Cabral
Marijuana and its major
psychoactive component, delta-9-tetrahydrocannabinol (THC), alter resistance to
bacterial, protozoan, and viral infections in vivo and in vitro.
These alterations have been accompanied by modifications in functional
components of the immune system. In addition, marijuana and THC, as well as
other cannabinoids, have been reported to directly affect functional activities
of lymphocytes, macrophages, natural killer cells, and other immunocytes. These
include effects on cytokine production resulting in a shift in the balance of
Th1 versus Th2 cytokines. Both receptor and non-receptor mediated modes of
action have been proposed as causative of cannabinoid effects. Reports that
marijuana and THC alter anti-microbial activity in vivo and in vitro
indicate that its use presents a potential risk of decreased resistance to
infections. However, few controlled longitudinal epidemiological and
immunological studies have been undertaken to correlate the immunosuppressive
effects of marijuana smoke or cannabinoids on the incidence of infections or
disease in humans.
KEYWORDS. AIDS, HIV,
cannabinoid receptors, cannabinoids, delta-9-tetrahydrocannabinol, immunity, infections,
marijuana, THC
Effects of Smoked Marijuana
on the Lung and Its Immune Defenses: Implications for Medicinal Use in
HIV-Infected Patients 87
Donald P. Tashkin
Habitual marijuana smoking
may cause a number of potentially harmful effects on the lung, including the
following: (1) acute and chronic bronchitis; (2) extensive histopathologic
alterations in the cells lining the bronchial passages that could impair
mucociliary clearance or predispose to malignancy; (3) increased accumulation
of inflammatory cells (alveolar macrophages) in the lung; and (4) impairment in
the function of these important immune-effector cells, including their ability
to kill microorganisms and to produce protective pro-inflammatory cytokines.
The major potential pulmonary consequences of habitual marijuana use are
pulmonary infection and respiratory cancer. Infectious complications could be
due to smoking-related damage to the mucociliary clearance mechanism,
marijuana-related impairment in the antimicrobial function of alveolar
macrophages and/or fungal or bacterial contamination of marijuana. Patients
with pre-existing immune deficits due to AIDS could be particularly susceptible
to pulmonary infectious complications of marijuana use.
KEYWORDS. Pulmonary
function, cannabis, medical marijuana, HIV, AIDS
Cannabis and Cannabis
Extracts: Greater Than the Sum of Their Parts? 103
John M. McPartland Ethan
B. Russo
A central tenet underlying
the use of botanical remedies is that herbs contain many active ingredients.
Primary active ingredients may be enhanced by secondary compounds, which act in
beneficial synergy. Other herbal constituents may mitigate the side effects of
dominant active ingredients. We reviewed the literature concerning medical
cannabis and its primary active ingredient, D9-tetrahydrocannabinol (THC). Good evidence shows that
secondary compounds in cannabis may enhance the beneficial effects of THC.
Other cannabinoid and non-cannabinoid compounds in herbal cannabis or its
extracts may reduce THC-induced anxiety, cholinergic deficits, and
immunosuppression. Cannabis terpenoids and flavonoids may also increase
cerebral blood flow, enhance cortical activity, kill respiratory pathogens, and
provide anti-inflammatory activity.
KEYWORDS. Cannabis,
marijuana, THC, cannabinoids, phytocannabinoids, cannabidiol, cannabichromene,
cannabibigerol, tetrahydrocannabivarin, terpenoids, essential oils, flavonoids,
herbal medicine, medicinal plants, herbal synergy
Harm Reduction Associated
with Inhalation and Oral Administration of Cannabis and THC 133
Franjo Grotenhermen
Inhalation of carcinogenic
combustion products associated with smoking is generally regarded as the major
health hazard in connection with the medical use of cannabis products.
Strategies to reduce respiratory and other adverse events resulting from this
common practice include relinquishment of inhalation and replacement by other
routes of administration, the use of plants with a high THC content allowing
reduction of the amount of smoked plant material, usage of inhalation devices
that improve the ratio of THC and tar, and avoidance of the Valsalva maneuver
that may cause spontaneous pneumothorax. The major risk associated with oral
cannabis use is accidental overdosage, especially in inexperienced users that
can be avoided by appropriate dosing procedures. A combination of oral use and
inhalation may be meaningful in several indications, decreasing the specific
risks of both routes. Preliminary studies using rectal, sublingual and
transdermal routes indicate that these alternatives to the two most common
forms of ingestion may be utilized medicinally in the future, further reducing
the possible risks associated with the administration of cannabis or single
cannabinoids.
KEYWORDS. Cannabis,
marijuana, THC, cannabinoids, smoking, inhalation, oral use, rectal use,
sublingual use, transdermal use, therapeutic use, side effects, health risk,
harm reduction, cancer, spontaneous pneumothorax, dosing, overdose, opium,
opiates, pharmacokinetics
Cannabis
"Vaporization": A Promising Strategy for Smoke Harm Reduction 153
Dale H. Gieringer
The primary health hazard
of medical cannabis is respiratory damage from marijuana smoke. Aside from oral
ingestion and other non-smoked delivery systems not yet commercially available,
strategies for reducing the harm of smoking include: (1) use of higher potency
cannabis and (2) smoking devices aimed at eliminating toxins from the smoke.
Studies have found that waterpipes and solid filters are ineffectual at
improving the THC/tar ratio in cannabis smoke. The most promising alternative
appears to be "vaporization," in which cannabis is heated to a point
where cannabinoids are emitted without combustion. A feasibility study by NORML
and MAPS has demonstrated that an electric vaporizer can successfully generate
THC at 185°C while completely suppressing benzene, toluene, and naphthalene
formation. Further studies are needed to evaluate how effectively vaporizers
suppress other toxins, and how their performance varies using different
samples, temperatures, and device designs.
KEYWORDS. Marijuana,
cannabis, smoke harm reduction, vaporizers, vaporization
Analgesic and Reinforcing
Properties of D9-THC-Hemisuccinate
in Adjuvant-Arthritic Rats 171
Susan L. Broom Kenneth
J. Sufka Mahmoud A. ElSohly Samir A. Ross
The use of D9-THC hemisuccinate (HS) in a suppository formulation
is an attempt to develop a cannabinoid possessing possible therapeutic effects
with a minimal side effect profile. The purpose of this study was to
investigate the antinociceptive and reinforcing effects of rectally
administered D9-THC-HS
in rats. Tests were conducted in two groups of animals: Complete Freund’s
adjuvant-inflamed animals (CFA) and non-inflamed controls. A hotplate test was
administered to index hyperalgesia and possible analgesic effects of D9-THC-HS on thermal nociception. CFA animals
demonstrated shorter latencies than non-inflamed animals. The highest dose of D9-THC-HS produced longer hotplate latencies.
Additionally, the reinforcing properties of D9-THC-HS were evaluated using the Conditioned Place
Preference (CPP) paradigm. D9-THC-HS produced an increase in preference scores in
non-inflamed animals (positive reinforcement), but did not affect preference
scores in CFA animals. These data suggest that D9-THC-HS has therapeutic potential and is unlikely to
possess an abuse liability when used in the context of chronic pain.
KEYWORDS. D9-THC, adjuvant-inflamed, rat, hotplate, conditioned
place preference
Prospects for New
Cannabis-Based Prescription Medicines 183
Brian A. Whittle
Geoffrey W. Guy Philip Robson
Cannabis is now emerging
from a period of prohibition and being revisited as a potential source of
treatments for conditions ill served by synthetic substances. Previous research
focussed primarily on effects produced by synthetic cannabinoids such as THC,
or cannabis of unknown cannabinoid content. Chemovars of cannabis characterized
by high content of specific cannabinoids (primarily, but not only THC and CBD)
have been developed. Clinical research using defined extracts from these
chemovars is now underway in the UK. Many diseases are multifactorial; a
variety of receptors need to be targeted to produce a therapeutic effect. A
defined botanical may better achieve this than a single synthetic compound as
the components can act synergistically. A new generation of cannabis based
medicinal products takes advantage of increasing understanding of the mode of
action of cannabinoids, evidence-based research on clinical uses and new
technology for realization of products, in anti-diversionary presentations.
KEYWORDS. Cannabinoids,
cannabis, CB receptors, new chemovars, clinical research, multiple sclerosis,
spinal cord injury, neurogenic pain, botanical extracts, secure dispensing,
alternative delivery systems, harm reduction