Scienza: Il THC diminuisce la pressione intraoculare e
migliora la circolazione del sangue nell’occhio
Secondo una ricerca dell’Università di Aachen una
dose orale singola di 7.5 mg di THC, applicata a 80 medici sani in un
auto-esperimento ha ridotto la pressione intraoculare (IOP) e aumentato il
flusso di sangue nella retina. Le misurazioni sono state fatte prima e dopo due
ore dall’assunzione
del THC.
Il THC ha determinato una riduzione significativa della
IOP da 13.2 mm Hg a 11.8 mm Hg in media. Il tempo per il passaggio di sangue
dalle arterie alle vene della retina è sceso significativamente da 1.77 secondi
a 1.57 secondi in media. La pressione arteriosa sistemica e il ritmo cardiaco
non sono stati significativamente alterati. I ricercatori concludono che
"i cannabinoidi, già noti per la loro capacità di ridurre la IOP, possono
migiorare l’emodinamica
della retina. Questo può essere benefico nei disturbi circolatori dell’occhio, incluso il
glaucoma."
Abstract
disponibile a: www.cannabis-med.org/studies/study.php
(Fonte:
Plange N, Arend KO, Kaup M, Doehmen B, Adams H, Hendricks S, Cordes A, Huth J,
Sponsel WE, Remky A. Dronabinol and retinal hemodynamics in humans. Am J
Ophthalmol 2007;143(1):173-4.)
RICERCA:
CANNABINOIDI E GLAUCOMA
La somministrazione attraverso la mucosa orale di estratti naturali a base di
THC riduce temporaneamente l’ipertensione intra-oculare dei malati di glaucoma,
secondo i risultati di uno studio pilota pubblicati sul numero di ottobre del
Journal of Glaucoma.
Sei pazienti con diagnosi di ipertensione intra-oculare (IO) o glaucoma
primitivo ad angolo aperto in stadio iniziale hanno partecipato in uno studio
randomizzato, controllato con placebo.
I ricercatori hanno misurato l’impatto di THC, CBD (cannabidiolo) o placebo
sulla pressione intra-oculare dei pazienti dopo una singola somministrazione.
La IO può causare danni al nervo ottico ed è considerata il principale fattore
di rischio nel glaucoma.
"Due ore dopo la somministrazione sublinguale di 5 mg di delta 9 THC, la
pressione intra-oculare era significativamente minore che dopo il placebo”,
hanno trovato gli scienziati “La pressione ritornò al valore iniziale dopo 4
ore.”
Inoltre i ricercatori riferiscono che una singola dose di CBD non aveva effetto
sulla IO a basse dosi (20 mg) mentre elevava la IO ad alte dosi (40 mg).
Studi clinici condotti all’Università di California a Los Angeles (UCLA) nel
1971 avevano per primi rilevato che la cannabis fumata riduceva temporaneamente
la pressione dell’occhio.
Fonte: Tomida I et al. "Effect of sublingual application of cannabinoids on
intraocular pressure: a pilot study'' Journal of Glaucoma. 2006;15(5):
349-53.
Effect
of Sublingual Application of Cannabinoids on Intraocular Pressure: A Pilot
Study.
Tomida I, Azuara-Blanco A,
House H, Flint M, Pertwee RG, Robson PJ.
*Department of Ophthalmology, Aberdeen Royal Infirmary section signSchool of
Medical Sciences, Institute of Medical Sciences, University of Aberdeen, UK
daggerCannabinoid Research Institute, Magdalen Centre, Oxford Science Park,
Oxford OX4 4GA double daggerGW Pharmaceuticals plc, Ely, Cambs CB7 4ZA.
PURPOSE: The purpose of this study was to assess the effect on intraocular
pressure (IOP) and the safety and tolerability of oromucosal administration of
a low dose of delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD).
PATIENTS AND METHODS: A randomized, double-masked, placebo-controlled, 4 way
crossover study was conducted at a single center, using cannabis-based
medicinal extract of Delta-9-THC and CBD. Six patients with ocular hypertension
or early primary open angle glaucoma received a single sublingual dose at 8 AM
of 5 mg Delta-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was
IOP. Secondary outcomes included visual acuity, vital signs, and psychotropic
effects. RESULTS: Two hours after sublingual administration of 5 mg
Delta-9-THC, the IOP was significantly lower than after placebo (23.5 mm Hg vs.
27.3 mm Hg, P=0.026). The IOP returned to baseline level after the 4-hour IOP
measurement. CBD administration did not reduce the IOP at any time. However,
the higher dose of CBD (40 mg) produced a transient elevation of IOP at 4 hours
after administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual
acuity were not significantly changed. One patient experienced a transient and
mild paniclike reaction after Delta-9-THC administration. CONCLUSIONS: A single
5 mg sublingual dose of Delta-9-THC reduced the IOP temporarily and was well
tolerated by most patients. Sublingual administration of 20 mg CBD did not
reduce IOP, whereas 40 mg CBD produced a transient increase IOP rise.
PMID: 16988594 [PubMed - as supplied by publisher]
|
2: Cell Mol Neurobiol.
2006 May 12; [Epub ahead of print] |
Implication of Cannabinoids in Neurological
Diseases.
Alsasua
Del Valle A.
Dpto. Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid,
Avda. Complutense s/n, Madrid, 28040, Spain, aalsasua@med.ucm.es.
1. Preparations from Cannabis sativa (marijuana) have been used for many
centuries both medicinally and recreationally.2. Recent advances in the
knowledge of its pharmacological and chemical properties in the organism,
mainly due to Delta(9)-tetrahydrocannabinol, and the physiological roles played
by the endocannabinoids have opened up new strategies in the treatment of
neurological and psychiatric diseases.3. Potential therapeutic uses of
cannabinoid receptor agonists include the management of spasticity and tremor
in multiple sclerosis/spinal cord injury, pain, inflammatory disorders,
glaucoma, bronchial asthma, cancer, and vasodilation that accompanies advanced
cirrhosis. CB(1) receptor antagonists have therapeutic potential in Parkinson's
disease.4. Dr. Julius Axelrod also contributed in studies on the neuroprotective
actions of cannabinoids.
PMID: 16699878 [PubMed - as supplied by publisher]
|
3: Handb Exp Pharmacol. 2005;(168):719-56. |
Human studies of cannabinoids and medicinal
cannabis.
Robson P.
Department of Psychiatry, Oxford University, Warneford Hospital, Oxford OX3
7JX, UK. pjr@gwpharm.com
Cannabis has been known as a medicine for several thousand years across many
cultures. It reached a position of prominence within Western medicine in the
nineteenth century but became mired in disrepute and legal controls early in
the twentieth century. Despite unremitting world-wide suppression, recreational
cannabis exploded into popular culture in the 1960s and has remained easily
obtainable on the black market in most countries ever since. This ready availability
has allowed many thousands of patients to rediscover the apparent power of the
drug to alleviate symptoms of some of the most cruel and refractory diseases
known to humankind. Pioneering clinical research in the last quarter of the
twentieth century has given some support to these anecdotal reports, but the
methodological challenges to human research involving a pariah drug are
formidable. Studies have tended to be small, imperfectly controlled, and have
often incorporated unsatisfactory synthetic cannabinoid analogues or smoked
herbal material of uncertain composition and irregular bioavailability. As a
result, the scientific evaluation of medicinal cannabis in humans is still in
its infancy. New possibilities in human research have been opened up by the
discovery of the endocannabinoid system, a rapidly expanding knowledge of
cannabinoid pharmacology, and a more sympathetic political environment in
several countries. More and more scientists and clinicians are becoming
interested in exploring the potential of cannabis-based medicines. Future
targets will extend beyond symptom relief into disease modification, and
already cannabinoids seem to offer particular promise in the treatment of
certain inflammatory and neurodegenerative conditions. This chapter will begin
with an outline of the development and current status of legal controls
pertaining to cannabis, following which the existing human research will be
reviewed. Some key safety issues will then be considered, and the chapter will
conclude with some suggestions as to future directions for human research.
Publication Types:
· Review
PMID: 16596794 [PubMed - indexed for MEDLINE]
|
4: J Ethnopharmacol. 2006 Apr 21;105(1-2):1-25. Epub 2006 Mar 15. |
Cannabinoids in medicine: A review of their
therapeutic potential.
Ben
Amar M.
Substance Abuse Program, Faculties of Continuing Education and Graduate
Studies, University of Montreal, C.P. 6128, succursale Centre-ville, Montreal,
Que. H3C 3J7, Canada. mohamed.ben.amar@umontreal.ca
In order to assess the current knowledge on the therapeutic potential of
cannabinoids, a meta-analysis was performed through Medline and PubMed up to
July 1, 2005. The key words used were cannabis, marijuana, marihuana, hashish,
hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol,
nabilone, levonantradol, randomised, randomized, double-blind, simple blind,
placebo-controlled, and human. The research also included the reports and
reviews published in English, French and Spanish. For the final selection, only
properly controlled clinical trials were retained, thus open-label studies were
excluded. Seventy-two controlled studies evaluating the therapeutic effects of
cannabinoids were identified. For each clinical trial, the country where the
project was held, the number of patients assessed, the type of study and
comparisons done, the products and the dosages used, their efficacy and their
adverse effects are described. Cannabinoids present an interesting therapeutic
potential as antiemetics, appetite stimulants in debilitating diseases (cancer
and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord
injuries, Tourette's syndrome, epilepsy and glaucoma.
PMID: 16540272 [PubMed - in process]
|
5: Ned Tijdschr Geneeskd.
2006 Jan 21;150(3):128-31. |
[The mechanism of action of cannabis and
cannabinoids]
[Article in Dutch]
Scholten WK.
wk.scholten@planet.nl
The effect ofcannabis can be explained on the basis of the function of the
cannabinoid receptor system, which consists of CB receptors (CB1, CB2),
endoligands to activate these receptors and an enzyme--fatty acid
amidohydrolase--to metabolize the endoligands. The endoligands of the
cannabinoid receptor system are arachidonic acid-like substances, and are
called endocannabinoids. Indications exist that the body also contains
arachidonic acid-like substances that inhibit fatty acid amido hydrolase.
Various cannabinoids have diverse effects on the receptors, functioning as
agonists, antagonists or partial antagonists, as well as affecting the vanilloid
receptor. Many known effects ofcannabis can be explained on the basis of this
mechanism of action as can the use ofcannabis in various conditions including
multiple sclerosis, Parkinson's disease, glaucoma, nausea, vomiting and
rheumatoid arthritis.
Publication Types:
· Review
PMID: 16463612 [PubMed - indexed for MEDLINE]
|
6: Am J Emerg Med.
2005 Oct;23(6):813-4. |
Bilateral angle-closure glaucoma after
combined consumption of "ecstasy" and marijuana.
Trittibach P, Frueh BE, Goldblum D.
Department of Ophthalmology, University of Bern, CH-3010 Bern, Switzerland.
Publication Types:
PMID: 16182995 [PubMed - indexed for MEDLINE]
|
7: P R Health Sci J.
2005 Mar;24(1):19-26. |
Recent developments in the therapeutic
potential of cannabinoids.
Corey S.
Department of Pharmacology and Toxicology, Institute of Neurobiology, Medical
Sciences Campus University of Puerto Rico, San Juan, Puerto Rico 00901.
scorey@neurobio.upr.clu.edu
OBJECTIVE: To examine the recent evidence that marijuana and other cannabinoids
have therapeutic potential. METHODS: Literature published since 1997 was
searched using the following terms: cannabinoid, marijuana, THC, analgesia,
cachexia, glaucoma, movement, multiple sclerosis, neurological, pain,
Parkinson, trial, vomiting. Qualifying clinical studies were randomized,
double-blind, and placebo-controlled. Selected open-label studies and surveys
are also discussed. RESULTS: A total of 15 independent, qualifying clinical
trials were identified, of which only three had more than 100 patients each.
Two large trials found that cannabinoids were significantly better than placebo
in managing spasticity in multiple sclerosis. Patients self-reported greater
sense of motor improvement in multiple sclerosis than could be confirmed
objectively. In smaller qualifying trials, cannabinoids produced significant
objective improvement of tics in Tourette's disease, and neuropathic pain. A
new, non-psychotropic cannabinoid also has analgesic activity in neuropathic
pain. No significant improvement was found in levodopa-induced dyskinesia in
Parkinson's Disease or post-operative pain. No difference from active placebo
was found for management of cachexia in a large trial. Some immune system
parameters changed in HIV-1 and multiple sclerosis patients treated with
cannabinoids, but the clinical significance is unknown. Quality of life
assessments were made in only three of 15 qualifying clinical trials.
CONCLUSION: Cannabinoids may be useful for conditions that currently lack
effective treatment, such as spasticity, tics and neuropathic pain. New
delivery systems for cannabinoids and cannabis-based medicinal extracts, as
well as new cannabinoid derivatives expand the options for cannabinoid therapy.
More well-controlled, large clinical tests are needed, especially with active placebo.
Publication Types:
· Review
PMID: 15895873 [PubMed - indexed for MEDLINE]
|
8: J
Glaucoma. 2005
Apr;14(2):175-7. |
Effects of marijuana on aqueous humor
dynamics in a glaucoma patient.
Zhan GL, Camras CB, Palmberg PF, Toris CB.
Department of Ophthalmology, University of Nebraska Medical Center, Omaha,
Nebraska 68198-5540, USA.
Publication Types:
PMID: 15741823 [PubMed - indexed for MEDLINE]
|
9: AIDS Policy Law. 2003 Oct
24;18(20):1. |
Justices mull medical marijuana laws.
[No authors listed]
Publication Types:
PMID: 14626967 [PubMed - indexed for MEDLINE]
|
10: Can
HIV AIDS Policy Law Rev. 2003 Apr;8(1):22-3. |
Troubled times for Canada's medical marijuana
program.
Thaczuk D.
Health Canada finally produces a good marijuana crop, but its medical marijuana
program is in a state of upheaval as it faces internal dissent regarding a
crucial aspect of its mandate, as well as fundamental challenges from the
courts. Meanwhile, the Justice Minister said that the government will introduce
legislation to decriminalize the possession of small amounts of marijuana.
Publication Types:
PMID: 12924290 [PubMed - indexed for MEDLINE]
|
11: Trans Am
Ophthalmol Soc. 2002;100:215-22; discussion 222-4. |
Delta-9-tetrahydrocannabinol (THC) in the treatment
of end-stage open-angle glaucoma.
Flach AJ.
Department of Veteran Affairs, Department of Ophthalmology, University of
California, San Francisco, USA.
PURPOSE: Evidence exists that the administration of cannabinoid derivatives can
lower intraocular pressure. Some patients with glaucoma believe they are being
deprived of a potentially beneficial treatment. Therefore, the Research
Advisory Panel of California instituted the Cannabis Therapeutic Research
Program to permit compassionate access to cannabinoid derivatives. Data about
the potential therapeutic usefulness and toxicity of these agents were
collected. This study reviews the results of this program with the specific aim
of providing further direction for these investigational efforts. METHODS: A
survey of local ophthalmologists indicated an impressive interest in
participating in and contributing patients with glaucoma unresponsive to
treatment to this study. Appropriate patients were treated with either orally
administered delta-9-tetrahydrocannabinol capsules or inhaled marijuana in
addition to their existing therapeutic regimen. RESULTS: Although 20 ophthalmologists
were approved as investigators, only nine patients were enrolled in the study.
An initial decrease in intraocular pressure was observed in all patients, and
the investigator's therapeutic goal was met in four of the nine patients.
However, the decreases in intraocular pressure were not sustained, and all
patients elected to discontinue treatment within 1 to 9 months for various
reasons. CONCLUSIONS: This uncontrolled, unmasked, nonrandomized study does not
permit definitive conclusions about the efficacy or toxicity of cannabinoids in
the treatment of glaucoma. There is an impression that this treatment can lower
intraocular pressure, but the development of tolerance and significant systemic
toxicity appears to limit the usefulness of this potential treatment. Both
patients and ophthalmologists greatly appreciated the opportunity to
participate in this study.
PMID: 12545695 [PubMed - indexed for MEDLINE]
|
12: J Public Health Policy.
2002;23(4):413-39. |
State medical marijuana laws: understanding
the laws and their limitations.
Pacula RL, Chriqui JF, Reichmann DA, Terry-McElrath YM.
RAND Corporation, 1700 Main Street, Santa Monica, California 90407, USA.
Significant attention has been given to the debate regarding allowances for
medical marijuana use since the 1996 California and Arizona ballot initiatives.
State medical marijuana allowances, however, have existed since the mid-1970s.
Much of the current debate stems from confusion about the various ways states
approach the issue. In this paper, we present original legal research on
current state medical marijuana laws identifying four different ways states
statutorily enable the medical use of marijuana. We discuss the tension these
approaches have with federal law as well as their implications regarding real
access for patients. In addition, we present information on how a small number
of states are trying to deal with the issue of access within the context of
their medical marijuana laws, and discuss the implication of various supply
approaches on the enforcement of other state marijuana laws.
PMID: 12532682 [PubMed - indexed for MEDLINE]
|
13: Ann Pharm Fr. 2002
Jul;60(4):271-3. |
[Cannabis therapy]
[Article in French]
Paris M.
Gambais, France
PMID: 12378155 [PubMed - indexed for MEDLINE]
|
14: Pain
Res Manag. 2001 Summer;6(2):80-91. |
Medicinal use of cannabis: history and
current status.
Kalant H.
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
harold.kalant@utoronto.ca
OBJECTIVE: To provide an overview of the history and pharmacology of cannabis
in relation to current scientific knowledge concerning actual and potential
therapeutic uses of cannabis preparations and pure cannabinoids. METHODS: The
literature on therapeutic uses of cannabis and cannabinoids was assessed with
respect to type of study design, quality and variability of data, independent
replications by the same or other investigators, magnitude of effects,
comparison with other available treatments and reported adverse effects. The
results of this review were also compared with those of major international
reviews of this topic in the past five years. CONCLUSIONS: Pure
tetrahydrocannabinol and several analogues have shown significant therapeutic
benefits in the relief of nausea and vomiting, and stimulation of appetite in
patients with wasting syndrome. Recent evidence clearly demonstrates analgesic
and anti-spasticity effects that will probably prove to be clinically useful. Reduction
of intraocular pressure in glaucoma and bronchodilation in asthma are not
sufficiently strong, long lasting or reliable to provide a valid basis for
therapeutic use. The anticonvulsant effect of cannabidiol is sufficiently
promising to warrant further properly designed clinical trials. There is still
a major lack of long term pharmacokinetic data and information on drug
interactions. For all the present and probable future uses, pure cannabinoids,
administered orally, rectally or parenterally, have been shown to be effective,
and they are free of the risks of chronic inflammatory disease of the airways
and upper respiratory cancer that are associated with the smoking of crude
cannabis. Smoking might be justified on compassionate grounds in terminally ill
patients who are already accustomed to using cannabis in this manner. Future
research will probably yield new synthetic analogues with better separation of
therapeutic effects from undesired psychoactivity and other side effects, and
with solubility properties that may permit topical administration in the eye,
or aerosol inhalation for rapid systemic effect without the risks associated
with smoke inhalation.
Publication Types:
PMID: 11854770 [PubMed - indexed for MEDLINE]
|
15: Duodecim.
1998;114(20):2115-20. |
[Cannabis and its effects on health]
[Article in Finnish]
Heinala P.
pekka.heinala@helsinki.fi
Publication Types:
· Review
PMID: 11717738 [PubMed - indexed for MEDLINE]
|
16: AIDS Policy Law. 1999 Oct
1;14(18):11. |
Legislature agrees to fund study of marijuana
efficacy.
[No authors listed]
AIDS: California could be the first State to conduct a research study on
medical uses for marijuana under the "Medical Research Act of 1999".
S.B. 847 would authorize a three-year program, administered by the University
of California, to study which methods of ingesting marijuana are most effective
in treating pain and side effects of treatments for AIDS, cancer, glaucoma and
seizures. The sponsor of the bill, Sen. John Vasconcellos, initially wanted $1
million in annual funding, but the program will be funded through the normal
appropriations process.
Publication Types:
PMID: 11367022 [PubMed - indexed for MEDLINE]
|
17: STEP Perspect. 1999 Summer;99(2):5. |
Medical marijuana: legal considerations.
Schouten JT.
AIDS: In 1998, Washington State passed a law, Initiative 692 (I-692), that gives
individuals who are charged with possession of marijuana for medical purposes a
possible affirmative defense. The law lets these individuals provide a note
from their doctor or a copy of their medical records stating they have a
condition that may benefit from the use of marijuana. I-692 does not legalize
the medical use of marijuana and does not affect Federal law, which makes
obtaining, possessing, and growing marijuana illegal. The Washington law limits
the amount of marijuana a patient can possess to a 60-day supply and defines
the conditions for which medical marijuana may be used. These conditions
include HIV, cancer, multiple sclerosis, and epilepsy.
Publication Types:
PMID: 11366751 [PubMed - indexed for MEDLINE]
|
18: AIDS Policy Law. 1999 Apr
30;14(8):12. |
Medical marijuana.
[No authors listed]
AIDS: The Florida Supreme Court heard oral arguments in April regarding a
glaucoma patient's request for a medical exception to the State prohibition on
use of marijuana. George Sowell was convicted on possession and cultivation
charges, and a trial judge refused to allow a medical necessity defense. A
State appeals court subsequently overturned Sowell's conviction. The case
focuses on whether the legislature intended to prohibit such a defense when it
declared in 1993 that the substance had no medicinal benefits.
Publication Types:
PMID: 11366533 [PubMed - indexed for MEDLINE]
|
19: Int J Neuropsychopharmacol. 1998 Jul;1(1):81-82. |
Comment on 'Health aspects of cannabis:
revisited' (Hollister).
Johnson BA.
Clinical Laboratory and Experimental Alcohol Research Center, Houston Health
Science Center, University of Texas-Houston, TX USA.
Dr. Leo Hollister's excellent article begins to address the need for better
understanding of the effects of cannabis use on health. The last five years in
the US have seen an increase in advocacy groups extolling the medicinal utility
of cannabis. On 5 November 1996, this culminated in California (proposition
215) joining the list of states permitting the limited use of cannabis for the
medicinal treatment of disorders including intractable pain, glaucoma, nausea
induced by chemotherapy for cancer or by AZT or Foscavir for the treatment of
AIDS, and for spasticity associated with multiple sclerosis (Burstein, 1997;
West and Homi, 1996; Grinspoon and Bakalar, 1995; Nahas and Manger, 1995). Of
these potential uses for cannabis, the evidence for the treatment of nausea and
the stimulation of appetite in cachetic patients appears most promising (for a
review see Voth and Schwartz, 1997). Yet not only do doubts remain about the
effectiveness of cannabis for the treatment of these conditions, since
definitive controlled clinical studies are typically lacking (Voelker, 1997),
but there is concern that any therapeutic advantage is more than offset by its
harmful effects. Within this context of increased medical sanction for the use
of cannabis in specific disease states for which it may have therapeutic
potential, evaluating its risks vs. benefits profile is essential to rational
prescribing. In addition, evaluating the public health risks associated with
reports of increased risks of cannabis use (Robertson et al., Poulton et al.,
1997), is of concern to advocates of its widespread legalization, governmental
agencies attempting to limit its promulgation, and to planners and providers of
health care charged with providing treatment for its consequences.
PMID: 11281948 [PubMed - as supplied by publisher]
|
20: An R Acad Nac Med
(Madr). 2000;117(3):595-605; discussion 616-24. |
[Potential therapeutic usefulness of cannabis
and cannabinoids]
[Article in Spanish]
Lorenzo Fernandez P.
Diseases in which Cannabis and cannabinoids have demonstrated some medicinal
putative properties are: nausea and vomiting associated with cancer
chemotherapy, muscle spasticity (multiple sclerosis, movement disorders), pain,
anorexia, epilepsy, glaucoma, bronchial asthma, neuroegenerative diseases,
cancer, etc. Although some of the current data comes from clinical controlled
essays, the majority are based on anecdotic reports. Basic pharmacokinetic and
pharmacodynamic studies and more extensive controlled clinical essays with
higher number of patients and long term studies are necessary to consider these
compounds useful since a therapeutical point of view.
Publication Types:
· Review
PMID: 11205042 [PubMed - indexed for MEDLINE]
|
21: Eur J Neurosci. 2001 Jan;13(2):409-12. |
The synthetic cannabinoid WIN55212-2
decreases the intraocular pressure in human glaucoma resistant to conventional
therapies.
Porcella
A, Maxia
C, Gessa
GL, Pani
L.
Center for Neuropharmacology C.N.R, B.B. Brodie Department of
Neuroscience, University of Cagliari, via Porcell 4, 09124-I Cagliari, Italy.
The search for new ocular hypotensive agents represents a frontier of current
eye research because blindness due to optic neuropathy occurs insidiously in
10% of all patients affected by glaucoma. Cannabinoids have been proposed to
lower intraocular pressure by either central or peripheral effects but a
specific mechanism for this action has never been elucidated. We recently
demonstrated the presence of the central cannabinoid receptor (CB(1)) mRNA and
protein in the human ciliary body. In the present study we show that the
synthetic CB(1) receptor agonist, WIN 55212--2, applied topically at doses of
25 or 50 microg (n = 8), decreases the intraocular pressure of human glaucoma
resistant to conventional therapies within the first 30 min (15 +/- 0.5% and 23
+/- 0.9%, respectively). A maximal reduction of 20 +/- 0.7% and 31 +/- 0.6%,
respectively, is reached in the first 60 min. These data confirm that CB(1)
receptors have direct involvement in the regulation of human intraocular
pressure, and suggest that, among various classes of promising antiglaucoma
agents, synthetic CB(1) receptor agonists should deserve further research and
clinical development.
Publication Types:
PMID: 11168547 [PubMed - indexed for MEDLINE]
|
22: Drugs.
2000 Dec;60(6):1303-14. |
Cannabinoids in clinical practice.
Williamson EM,
Evans FJ.
Centre for Pharmacognosy, The School of Pharmacy, University of London,
England.
Cannabis has a potential for clinical use often obscured by unreliable and
purely anecdotal reports. The most important natural cannabinoid is the
psychoactive tetrahydrocannabinol (delta9-THC); others include cannabidiol
(CBD) and cannabigerol (CBG). Not all the observed effects can be ascribed to
THC, and the other constituents may also modulate its action; for example CBD reduces
anxiety induced by THC. A standardised extract of the herb may be therefore be
more beneficial in practice and clinical trial protocols have been drawn up to
assess this. The mechanism of action is still not fully understood, although
cannabinoid receptors have been cloned and natural ligands identified. Cannabis
is frequently used by patients with multiple sclerosis (MS) for muscle spasm
and pain, and in an experimental model of MS low doses of cannabinoids
alleviated tremor. Most of the controlled studies have been carried out with
THC rather than cannabis herb and so do not mimic the usual clincal situation.
Small clinical studies have confirmed the usefulness of THC as an analgesic;
CBD and CBG also have analgesic and antiinflammatory effects, indicating that
there is scope for developing drugs which do not have the psychoactive
properties of THC. Patients taking the synthetic derivative nabilone for
neurogenic pain actually preferred cannabis herb and reported that it relieved
not only pain but the associated depression and anxiety. Cannabinoids are
effective in chemotherapy-induced emesis and nabilone has been licensed for
this use for several years. Currently, the synthetic cannabinoid HU211 is
undergoing trials as a protective agent after brain trauma. Anecdotal reports
of cannabis use include case studies in migraine and Tourette's syndrome, and
as a treatment for asthma and glaucoma. Apart from the smoking aspect, the
safety profile of cannabis is fairly good. However, adverse reactions include panic
or anxiety attacks, which are worse in the elderly and in women, and less
likely in children. Although psychosis has been cited as a consequence of
cannabis use, an examination of psychiatric hospital admissions found no
evidence of this, however, it may exacerbate existing symptoms. The relatively
slow elimination from the body of the cannabinoids has safety implications for
cognitive tasks, especially driving and operating machinery; although driving
impairment with cannabis is only moderate, there is a significant interaction
with alcohol. Natural materials are highly variable and multiple components
need to be standardised to ensure reproducible effects. Pure natural and
synthetic compounds do not have these disadvantages but may not have the overall
therapeutic effect of the herb.
Publication Types:
· Review
PMID: 11152013 [PubMed - indexed for MEDLINE]
|
23: Forsch Komplementarmed.
1999 Oct;6 Suppl 3:28-36. |
[Results of a standardized survey on the
medical use of cannabis products in the German-speaking area]
[Article in German]
Schnelle M, Grotenhermen F,
Reif M, Gorter RW.
Europaisches Institut fur
onkologische und immunologische Forschung, Berlin, Deutschland.
The plant Cannabis sativa has a long history of medical use in the treatment
of pain and spasms, the promotion of sleep, and the suppression of nausea and
vomiting. However, in the early 70s cannabis was classified in the Narcotic
Acts in countries all over the world as having no therapeutic benefit;
therefore, it cannot be prescribed by physicians or dispensed by pharmacists.
In the light of this contradictory situation an increasing number of patients
practices a self-prescription with cannabis products for relieving a variety of
symptoms. An anonymous standardized survey of the medical use of cannabis and
cannabis products of patients in Germany, Austria and Switzerland was conducted
by the Association for Cannabis as Medicine (Cologne, Germany). During about
one year 170 subjects participated in this survey; questionnaires of 128
patients could be included into the evaluation. 68% of these participants were
males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most
frequently mentioned indications for medicinal cannabis use were depression
(12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%),
asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders
(4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%),
glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury
(2.4%). The majority of patients used natural cannabis products such as
marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol
(Marinol) was taken by prescription. About half of the 128 participants of the
survey (52.4%) had used cannabis as a recreational drug before the onset of
their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in
36.5% of cases both application modes were used. 72.2% of the patients stated
the symptoms of their illness to have 'much improved' after cannabis ingestion,
23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6%
described that their symptoms got 'worse'. Being asked for the satisfaction
with their therapeutic use of cannabis 60.8% stated to be 'very satisfied',
24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'.
70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong'
side effects. 84.1% of patients have not felt any need for dose escalation
during the last 3 months, 11.0% had to increase their cannabis dose
'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects.
Thus, this survey demonstrates a successful use of cannabis products for the
treatment of a multitude of various illnesses and symptoms. This use was
usually accompanied only by slight and in general acceptable side effects.
Because the patient group responding to this survey is presumably highly
selected, no conclusions can be drawn about the quantity of wanted and unwanted
effects of the medicinal use of the hemp plant for particular indications.
Copyright Copyright 1999 S. Karger GmbH, Freiburg
PMID: 10575286 [PubMed - indexed for MEDLINE]
|
24: Forsch Komplementarmed.
1999 Oct;6 Suppl 3:12-5. |
Cannabis and cannabinoids: pharmacology and
rationale for clinical use.
Pertwee RG.
Institute of Biomedical Sciences, Aberdeen, Scotland. rgp@aberdeen.ac.uk
It is now known that there are at least two types of cannabinoid receptors.
These are CB1 receptors, present mainly on central and peripheral neurones, and
CB2 receptors, present mainly on immune cells. Endogenous cannabinoid receptor
agonists ('endocannabinoids') have also been identified. The discovery of this
'endogenous cannabinoid system' has led to the development of selective CB1 and
CB2 receptor ligands and fueled renewed interest in the clinical potential of
cannabinoids. Two cannabinoid CB1 receptor agonists are already used
clinically, as antiemetics or as appetite stimulants. These are D 9 -
tetrahydrocannabinol (THC) and nabilone. Other possible uses for CB1 receptor
agonists include the suppression of muscle spasm/spasticity associated with
multiple sclerosis or spinal cord injury, the relief of chronic pain and the
management of glaucoma and bronchial asthma. CB1 receptor antagonists may also
have clinical applications, e. g. as appetite suppressants and in the
management of schizophrenia or disorders of cognition and memory. So too may
CB2 receptor ligands and drugs that activate cannabinoid receptors indirectly
by augmenting endocannabinoid levels at cannabinoid receptors. When taken
orally, THC seems to undergo variable absorption and to have a narrow
'therapeutic window' (dose range in which it is effective without producing
significant unwanted effects). This makes it difficult to predict an oral dose
that will be both effective and tolerable to a patient and indicates a need for
better cannabinoid formulations and modes of administration. For the
therapeutic potential of cannabis or CB1 receptor agonists to be fully
exploited, it will be important to establish objectively and conclusively (a)
whether these agents have efficacy against selected symptoms that is of clinical
significance and, if so, whether the benefits outweigh the risks, (b) whether
cannabis has therapeutic advantages over individual cannabinoids, (c) whether
there is a need for additional drug treatments to manage any of the disorders
against which cannabinoids are effective, and (d) whether it will be possible
to develop drugs that have reduced psychotropic activity and yet retain the
ability to act through CB1 receptors to produce their sought-after effects.
Copyright Copyright 1999 S. Karger GmbH, Freiburg
Publication Types:
· Review
PMID: 10575283 [PubMed - indexed for MEDLINE]
|
25: Brain Res Mol Brain Res.
1998 Jul 15;58(1-2):240-5. |
Cannabinoid receptor CB1 mRNA is highly
expressed in the rat ciliary body: implications for the antiglaucoma properties
of marihuana.
Porcella
A, Casellas
P, Gessa
GL, Pani
L.
Center for Neuropharmacology, C.N.R. and "B.B. Brodie"
Department of Neuroscience, University of Cagliari, via Porcell, 4, 09124-I
Cagliari, Italy.
We used RT-PCR to measure relative differences in cannabinoid receptor (CB)
mRNAs in the rat eye, comparing CB1 or CB2 transcripts to that of the
normalizing reference gene beta2 microglobulin (beta2m). Significantly higher
levels of CB1 mRNA levels were found in the ciliary body (0.84+/-0.05% of
beta2m) than in the iris, (0.34+/-0.04% of beta2m), retina (0.07+/-0.005% of
beta2m) and choroid (0.06+/-0.005% of beta2m). CB2 mRNA was undetectable. This
expression pattern supports a specific role for the CB1 receptor in controlling
intraocular pressure, helping to explain the antiglaucoma property of
cannabinoids. Copyright 1998 Elsevier Science B.V. All rights reserved.
PMID: 9685662 [PubMed - indexed for MEDLINE]
|
26: West J Med. 1998
Jun;168(6):540-3. |
Medical marijuana.
Marmor JB.
Department of Radiation Oncology, Sequoia Hospital, Redwood City California
94062-2799, USA. jbm@marmor.org
Although many clinical studies suggest the medical utility of marijuana for
some conditions, the scientific evidence is weak. Many patients in California
are self-medicating with marijuana, and physicians need data to assess the
risks and benefits. The only reasonable solution to this problem is to
encourage research on the medical effects of marijuana. The current regulatory
system should be modified to remove barriers to clinical research with
marijuana. The NIH panel has identified several conditions for which there may
be therapeutic benefit from marijuana use and that merit further research.
Marijuana should be held to the same evaluation standards of safety and
efficacy as other drugs (a major flaw in Proposition 215) but should not have
to be proved better than current medications for its use to be adopted. The
therapeutic window for marijuana and THC between desired effect and unpleasant
side effects is narrow and is a major reason for discontinuing use. Although
the inhaled route of administration has the benefit of allowing patients to
self-titrate the dose, the smoking of crude plant material is problematic. The
NIH panel recommended that a high priority be given to the development of a
controlled inhaled form of THC. The presence of a naturally occurring
cannabinoid-receptor system in the brain suggests that research on selective
analogues of THC may be useful to enhance its therapeutic effects and minimize
adverse effects.
Publication Types:
·
Review
PMID: 9656007 [PubMed - indexed for MEDLINE]
|
27: J
Am Pharm Assoc (Wash). 1998 Mar-Apr;38(2):220-7. |
Comment in:
·
J Am Pharm Assoc (Wash). 1998
Mar-Apr;38(2):126.
Analysis
of the medical use of marijuana and its societal implications.
Taylor HG.
Sparrow Hospital, Lansing, Michigan 48826, USA. hgtaylor@pilot.msu.edu
OBJECTIVE: To review the pharmacology, therapeutics, adverse effects, and
societal implications of the medical use of marijuana. DATA SOURCES: MEDLINE
and manual searches of English-language marijuana literature, supplemented with
interviews of scientists currently conducting cannabinoid research. Search
terms included pain OR palliative care AND cannabis or ALL marijuana; cachexia
OR appetite OR appetite stimulants; muscle spasticity OR spasm; immune system
and cannabis; nausea and vomiting and cancer and cannabis. MEDLINE search
terms: cannabis OR marijuana smoking OR marijuana abuse; all glaucoma; multiple
sclerosis AND cannabis OR marijuana smoking OR marijuana abuse. STUDY
SELECTION: Studies on pharmacology, risks, and medical potential of marijuana.
DATA EXTRACTION: Not applicable. DATA SYNTHESIS: The most prominent effects of
marijuana are mediated by receptors in the brain. Acute intoxication is
characterized by euphoria, loss of short-term memory, stimulation of the
senses, and impaired linear thinking. Depersonalization and panic attacks are
adverse effects. Increased heart rate and reddened conjunctivae are common
physical effects. Chronic, high doses may cause subtle impairment of cognitive
abilities that are appear to be long-term, but of unknown duration. Marijuana
may be a risk factor for individuals with underlying mental illness. It causes
dependence, but compared with cocaine, alcohol, heroin, and nicotine, marijuana
has little addictive power and produces only mild withdrawal symptoms.
Marijuana shows clinical promise for glaucoma, nausea and vomiting, analgesia,
spasticity, multiple sclerosis, and AIDS wasting syndrome. CONCLUSION: As a
recreational drug, marijuana poses dangers, particularly to social and
emotional development during adolescence and young adulthood. As a medical
drug, marijuana should be available for patients who do not adequately respond
to currently available therapies.
Publication Types:
·
Review
PMID: 9654850 [PubMed - indexed for MEDLINE]
|
28: Ned Tijdschr Geneeskd.
1997 Aug 30;141(35):1689-93. |
[Therapeutic applications and biomedical effects
of cannabinoids; pharmacological starting points]
[Article in Dutch]
Killestein J, Nelemans SA.
Rijksuniversiteit, Groningen Institute for Drug Studies (GIDS).
A broad range of therapeutic applications has been suggested for cannabis or
its pharmacologically active compound (tetrahydrocannabinol; THC) in many
publications. Psychotropic side effects and the anecdotal character of the
research have limited the pharmacotherapeutic use of THC until now. Therefore,
the Netherlands Health Council recently decided negatively on this matter.
Besides several cannabinoid receptor subtypes present in the central nervous
system and peripheral tissues endogenous cannabinoids have been detected. These
endogenous cannabinoids appear to play an important role in signal
transduction, which may be starting points for therapy regarding:
cardiovascular diseases, multiple sclerosis and spinal cord disorders.
cerebrovascular accident and brain trauma, neurodegenerative diseases,
epilepsy, pain management, glaucoma, oncologic and aids-related disorders such
as nausea, vomiting and appetite problems.
Publication Types:
· Review
PMID: 9543785 [PubMed - indexed for MEDLINE]
|
29: Ann Intern Med. 1997 May
15;126(10):791-8. |
Comment in:
·
ACP J
Club. 1997 Nov-Dec;127(3):65.
·
Ann Intern Med. 1997 Dec
15;127(12):1134-5.
·
Ann Intern Med. 1997 Dec
15;127(12):1134; author reply 1135.
·
Ann Intern Med. 1997 Dec
15;127(12):1134; author reply 1135.
Medicinal
applications of delta-9-tetrahydrocannabinol and marijuana.
Voth EA, Schwartz RH.
International Drug Strategy Institute, Topeka, Kansas, USA.
The use of crude marijuana for herbal medicinal applications is now being
widely discussed in both the medical and lay literature. Ballot initiatives in
California and Arizona have recently made crude marijuana accessible to
patients under certain circumstances. As medicinal applications of pure forms
of delta-9-tetrahydrocannabinol (THC) and crude marijuana are being considered,
the most promising uses of any form of THC are to counteract the nausea
associated with cancer chemotherapy and to stimulate appetite. We evaluated the
relevant research published between 1975 and 1996 on the medical applications,
physical complications, and legal precedents for the use of pure THC or crude
marijuana. Our review focused on the medical use of THC derivatives for nausea
associated with cancer chemotherapy, glaucoma, stimulation of appetite, and
spinal cord spasticity. Despite the toxicity of THC delivered in any form,
evidence supports the selective use of pure THC preparations to treat nausea
associated with cancer chemotherapy and to stimulate appetite. The evidence
does not support the reclassification of crude marijuana as a prescribable
medicine.
Publication Types:
·
Review
PMID: 9148653 [PubMed - indexed for MEDLINE]
|
30: JAMA.
1997 Mar 19;277(11):867-8. |
NIH
panel says more study is needed to assess marijuana's medicinal use.
Voelker R.
Publication Types:
·
News
PMID: 9062309 [PubMed - indexed for MEDLINE]
|
31: AIDS Treat News. 1996 Oct 18;(No
257):1-3. |
Medical marijuana: the state of the research.
Mirken B.
AIDS: Recent raids on buyers' clubs in San Francisco have focused attention on
medicinal uses of marijuana. The Clinton administration's policy is that there
is no scientific evidence that smoked marijuana is useful in treating pain and
nausea in AIDS and cancer patients. However, mainstream medical literature has
supported the use of cannabis in managing symptoms of diseases such as glaucoma
and multiple sclerosis. Well designed, controlled studies of marijuana are
needed to determine the effective medical uses of the drug and break the
political stalemate on this issue.
Publication Types:
PMID: 11363931 [PubMed - indexed for MEDLINE]
|
32: AIDS Policy Law. 1995 Jun
16;10(11):2. |
Medical
association supports studies on marijuana therapy.
[No authors listed]
AIDS: The Gay and Lesbian Medical Association (GLMA) issued a statement on May
19, 1995, announcing its support of clinical trials of the therapeutic uses of
marijuana. The U.S. Department of Health and Human Services has continued to
resist permitting clinical trials of marijuana despite evidence that it can
relieve symptoms of cancer, multiple sclerosis, and glaucoma. According to Dr.
Alvin Novick, head of GLMA's AIDS Task Force, the Clinton Administration is
being asked to not let its political fears blind it to the positive and
legitimate scientific research designed to alleviate the suffering of thousands
of AIDS patients.
Publication Types:
PMID: 11362532 [PubMed - indexed for MEDLINE]
|
33: J Natl Cancer Inst.
1992 Apr 1;84(7):475-6. |
PHS
cancels availability of medicinal marijuana.
Bowersox J.
Publication Types:
·
News
PMID: 1545433 [PubMed - indexed for MEDLINE]
|
34: Int J Addict.
1986 Apr-May;21(4-5):579-87. |
Interview
with Prof. Raphael Mechoulam, codiscoverer of THC.. Interview by Stanley
Einstein.
Mechoulam R.
Publication Types:
PMID: 3021637 [PubMed - indexed for MEDLINE]
|
35: Pharmacol Rev. 1986
Mar;38(1):1-20. |
Health
aspects of cannabis.
Hollister LE.
Marijuana seems firmly established as another social drug in Western countries,
regardless of its current legal status. Patterns of use vary widely. As with
other social drugs, the pattern of use is critical in determining adverse
effects on health. Perhaps the major area of concern about marijuana use is
among the very young. Using any drug on a regular basis that alters reality may
be detrimental to the psychosocial maturation of young persons. Chronic use of
marijuana may stunt the emotional growth of youngsters. Evidence for an
amotivational syndrome is largely based on clinical reports; whether marijuana
use is a cause or effect is uncertain. A marijuana psychosis, long rumored, has
been difficult to prove. No one doubts that marijuana use may aggravate
existing psychoses or other severe emotional disorders. Brain damage has not
been proved. Physical dependence is rarely encountered in the usual patterns of
social use, despite some degree of tolerance that may develop. The endocrine
effects of the drug might be expected to delay puberty in prepubertal boys, but
actual instances have been rare. As with any material that is smoked, chronic
smoking of marijuana will produce bronchitis; emphysema or lung cancer have not
yet been documented. Cardiovascular effects of the drug are harmful to those
with preexisting heart disease; fortunately the number of users with such
conditions is minimal. Fears that the drug might accumulate in the body to the
point of toxicity have been groundless. The potential deleterious effects of
marijuana use on driving ability seem to be self-evident; proof of such
impairment has been more difficult. The drug is probably harmful when taken
during pregnancy, but the risk is uncertain. One would be prudent to avoid
marijuana during pregnancy, just as one would do with most other drugs not
essential to life or well-being. No clinical consequences have been noted from
the effects of the drug on immune response, chromosomes, or cell metabolites.
Contamination of marijuana by spraying with defoliants has created the clearest
danger to health; such attempts to control production should be abandoned.
Therapeutic uses for marijuana, THC, or cannabinoid homologs are being actively
explored. Only the synthetic homolog, nabilone, has been approved for use to
control nausea and vomiting associated with cancer chemotherapy.(ABSTRACT
TRUNCATED AT 400 WORDS)
Publication Types:
·
Review
PMID: 3520605 [PubMed - indexed for MEDLINE]
|
36: Bull Narc. 1985 Oct-Dec;37(4):3-13. |
An
update on cannabis research.
Husain S, Khan I.
A symposium of over 125 scientists, held in August 1984 at the campus of Oxford
University, considered the latest developments concerning cannabis research.
Evidence on the mode of tetrahydrocannabinol action on the central nervous
system indicates that acetylcholine turnover in the hippocampus through a
GABA-ergic mechanism is of major importance, though the role of the
dopaminergic or serotoninergic mechanism and involvement of prostaglandins and
c-AMP is not ruled out. The use of cannabis causes prominent and predictable
effects on the heart, including increased work-load, increased plasma volume
and postural hypotension, which could impose threats to the cannabis users with
hypertension, cerebrovascular disease or coronary arteriosclerosis. Cannabis or
tetrahydrocannabinol has damaging effects on the endocrine functions in both
male and female of all animal species tested. Among possible mechanisms of
action, it is suggested that tetrahydrocannabinol disrupts gonadal functions by
depriving the testicular cells of their energy reserves by inhibition of
cellular energetics, and that it stimulates androgen-binding protein secretion,
which may account for oligospermia seen in chronic cannabis smokers. In
addition to these direct effects on gonads, tetrahydrocannabinol interferes
with hormonal secretions from the pituitary, including luteinizing hormones,
follicle-stimulating hormones and prolactin. Research findings indicate that
maternal and paternal exposure to cannabinoids can influence developmental and
reproductive functions in the offspring, but it is difficult to separate
possible teratogenic effects from subsequent gametotoxic and mutagenic
potentials of cannabinoids.
Publication Types:
·
Review
PMID: 3914916 [PubMed - indexed for MEDLINE]
|
37: Int J Addict.
1985 May;20(5):691-9. |
Therapeutic
issues of marijuana and THC (tetrahydrocannabinol).
Ungerleider JT, Andrysiak T.
This article summarizes current knowledge about the medicinal value of cannabis
and its principal psychoactive ingredient, delta 9-tetrahydrocannabinol (THC),
particularly in the control of nausea and vomiting, in glaucoma, and in
reduction of spasticity in multiple sclerosis. The major issues in the
controversy about marijuana and medicine, primarily moral and ethical, are
discussed.
PMID: 2995262 [PubMed - indexed for MEDLINE]
|
38: Curr Eye Res. 1984 Jun;3(6):841-50. |
Cannabinoids
in glaucoma II: the effect of different cannabinoids on intraocular pressure of
the rabbit.
ElSohly
MA, Harland
EC, Benigni
DA, Waller
CW.
Thirty-two different
cannabinoids were tested for their ability to reduce intraocular pressure (IOP)
in the rabbit. These included many of delta 9- and delta 8-THC derivatives and
metabolites along with other natural and synthetic cannabinoids. In addition,
some non-cannabinoid constituents of Cannabis were screened using the same
model. All compounds were administered intravenously, while only a few were
tested topically in mineral oil. Water soluble derivatives of delta 9- and
delta 8-THC were prepared and tested topically in aqueous solution. The data
revealed that certain derivatives of delta 9-and delta 8-THC were more active
in lowering IOP than the parent cannabinoids. In addition, compounds other than
delta 9- and delta 8-THC and their derivatives were shown to have activity.
PMID: 6329602 [PubMed - indexed for MEDLINE]
|
39: Drug Alcohol Depend. 1983
Apr;11(2):135-45. |
Cannabis:
finally a therapeutic agent?
Hollister LE.
PMID: 6305618 [PubMed - indexed for MEDLINE]
|
40: Med Res Rev. 1983
Apr-Jun;3(2):119-46. |
Drugs related to tetrahydrocannabinol.
Razdan RK, Howes JF.
Publication Types:
· Review
PMID: 6134882 [PubMed - indexed for MEDLINE]
|
: Fortschr Med. 1982 Mar
4;100(9):343-6. |
[Cannabis and cannabinoids. Possibilities of
their therapeutic use]
[Article in German]
Heim ME.
Newer aspects of therapeutic potentials of cannabis and cannabinoids are
reviewed. The major active constituent of cannabis sativa,
delta-9-tetrahydrocannabinol and synthetic cannabinoids are evaluated in
several clinical trials on their antiemetic efficacy in cancer chemotherapy
induced vomiting. 80% of patients refractory to standard antiemetic treatment
could be improved with the synthetic cannabinoid levonantradol. Other
therapeutic effects, which are presently investigated in clinical trials are
analgesia, antispasticity, anticonvulsion and the reduction of intraocular
pressure in glaucoma. The future goal of cannabinoid research is the separation
between specific pharmacologic activities and undesirable psychotropic effects.
PMID: 7076098 [PubMed - indexed for MEDLINE]
|
42: J Clin Pharmacol. 1981
Aug-Sep;21(8-9 Suppl):467S-471S. |
Topical
delta 9-tetrahydrocannabinol and aqueous dynamics in glaucoma.
Merritt JC, Perry DD, Russell DN, Jones BF.
Systemic delta 9-tetrahydrocannabinol (THC), administered either by smoking
marihuana or as synthetic THC in soft gelatin capsules, lowers ocular tension
in various glaucomas, but at the expense of significant decreases in systolic
blood pressure. Topical THC in light mineral oil vehicles, though effective in
laboratory animals, was not shown effective in 0.05 and 0.1% topical solutions
when administered to six subjects with primary open-angle glaucoma in a
randomized, balanced, double-masked protocol. Light mineral oil, which has an
affinity for corneal epithelium, is an optimum vehicle for administering drugs
whose mechanisms of action are systemic rather than local within the eye.
Further glaucoma research should therefore proceed with marihuanas containing insignificant
levels of THC (less than 0.4%) and with various local delivery systems of the
ocular-active cannabinoid found in Cannabis sativa.
Publication Types:
PMID: 6271841 [PubMed - indexed for MEDLINE]
|
43: J Clin Pharmacol. 1981
Aug-Sep;21(8-9 Suppl):201S-207S. |
The
clinical pharmacology and dynamics of marihuana cigarette smoking.
Perez-Reyes M, Owens SM, Di Guiseppi S.
We have studied the dynamics of marihuana smoking, the plasma concentration of
delta 9-tetrahydrocannabinol (THC), and the pharmacologic effects produced by
the sequential smoking of two 1% marihuana cigarettes at a 2-hour interval.
Three males and three females, experienced marihuana smokers, participated in
the study. The results indicate that each subject smoked his or her two
cigarettes at a similar rate. The THC plasma concentrations produced by the smoking
of the second cigarette were slightly lower than those produced by the first
cigarette. The levels of the psychologic "high" caused by the two
cigarettes were similar. However, the first cigarette accelerated the heart
twice as much as the second cigarette. Between males and females there were
marked differences in the rate at which the cigarettes were smoked. In
particular, males took more puffs, took them more often, and consumed the
cigarettes more rapidly than females. The plasma concentrations of THC, the
self-reported psychologic effects, and the heart rate acceleration produced by
the smoking of the two cigarettes were identical between the sexes.
PMID: 6271825 [PubMed - indexed for MEDLINE]
|
44: J Clin Pharmacol. 1981
Aug-Sep;21(8-9 Suppl):143S-152S. |
Clinical
relevance of cannabis tolerance and dependence.
Jones RT, Benowitz NL, Herning RI.
Psychoactive drugs are often widely used before tolerance and dependence is
fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic
changes, decreased intraocular pressure, sleep and sleep EEG, mood and
behavioral changes is acquired and, to a great degree, lost rapidly with
optimal conditions. Mechanisms appear more functional than metabolic.
Acquisition rate depends on dose and dose schedule. Dependence, manifested by
withdrawal symptoms after as little as 7 days of THC administration, is
characterized by irritability, restlessness, insomnia, anorexia, nausea,
sweating, salivation, increased body temperature, altered sleep and waking EEG,
tremor, and weight loss. Mild and transient in the 120 subjects studied, the
syndrome was similar to sedative drug withdrawal. Tolerance to drug side
effects can be useful. Tolerance to therapeutic effects or target symptoms
poses problems. Clinical significance of dependence is difficult to assess
since drug-seeking behavior has many determinants. Cannabis-induced super
sensitivity should be considered wherever chronic drug administration is
anticipated in conditions like epilepsy, glaucoma or chronic pain. Cannabis
pharmacology suggests ways of minimizing tolerance and dependence problems.
PMID: 6271820 [PubMed - indexed for MEDLINE]
|
45: J Clin Pharmacol. 1981
Aug-Sep;21(8-9 Suppl):113S-121S. |
THC therapeutic research by independent and
state-sponsored investigators: a historical review.
Scigliano JA.
A brief history of the control and use of cannabis in the United States is presented.
Essential to the discussion are the federal law: the Marihuana Tax Stamp Act of
1937; the Controlled Substances Act of 1970; and the Federal Food, Drug and
Cosmetic Act of 1962. On mandate of Congress in 1968, initial studies were
directed to determine effects of long-term use in man. The annual reporting of
the status of "Marihuana and Health" was established. In the early
1970s, the scope of research was broadened to include evaluation of THC for use
in certain medical conditions. Interest in therapeutic research may have been
influenced by anecdotal reports of benefit for nausea and vomiting of cancer
chemotherapy and for elevated intraocular pressure of glaucoma, by the lobbying
for laws to legalize marihuana by special interest groups, and by the passage
of state "Controlled Substances Therapeutic Research" acts (CSTRA). A
listing of approved INDs in four therapeutic categories, a chart comparing the
components of laws passed by 25 states, and a bibliography of suggested reading
for further contact with the subject matter are included.
Publication Types:
PMID: 6271816 [PubMed - indexed for MEDLINE]
|
46: Clin Toxicol. 1981 Feb;18(2):245-6. |
Reports
of marijuana for glaucoma treatment are misleading; researchers will study.
National Institutes of Health.
[No authors listed]
Publication Types:
·
News
PMID: 7226736 [PubMed - indexed for MEDLINE]
|
47: Biochem Pharmacol. 1981 Jan
15;30(2):103-6. |
Recent
advances in antiglaucoma drugs.
Chiou GC.
PMID: 7248025 [PubMed - indexed for MEDLINE]
|
48: J Pharm Pharmacol.
1981 Jan;33(1):40-1. |
Topical
delta 9-tetrahydrocannabinol in hypertensive glaucomas.
Merritt JC, Olsen JL, Armstrong JR, McKinnon SM.
PMID: 6114151 [PubMed - indexed for MEDLINE]
|
49: JAMA.
1980 Dec 5;244(22):2500. |
No
green light for grass in glaucoma.
Gonzalez ER.
Publication Types:
·
News
PMID: 7431581 [PubMed - indexed for MEDLINE]
|
50: Ann Ophthalmol. 1980 Apr;12(4):448,
50. |
Efficacy
in glaucoma treatment--the potential of marijuana.
Gaasterland DE.
Publication Types:
PMID: 7235473 [PubMed - indexed for MEDLINE]
|
51: Ophthalmology. 1980 Mar;87(3):222-8. |
Effect
of marihuana on intraocular and blood pressure in glaucoma.
Merritt JC, Crawford WJ, Alexander PC, Anduze AL, Gelbart SS.
Marihuana inhalation was accompanied by increased heart rate and decreased
intraocular and blood pressure in 18 subjects with heterogenous glaucomas. The hypotensive
effects appeared in 60 to 90 minutes as the decrease in intraocular pressure
(IOP) appeared to follow the decrease in blood pressure. In addition to any
local effect, the mechanism of lowered to any local effect, the mechanism of
lowered IOP may also involve the decreased pressure perfusing the ciliary body
vasculature as a result of the peripheral vasodilatory properties of marihuana.
Postural hypotension, tachycardia, palpitations, and alterations in mental
status occurred with such frequency as to mitigate against the routine used in
the general glaucoma population. Our data indicate that further research should
be directed to local means of delivering the ocular hypotensive cannabinoid to
the glaucomatous eye.
Publication Types:
PMID: 7053160 [PubMed - indexed for MEDLINE]
|
52: J Tenn Med Assoc.
1980 Mar;73(3):187-9. |
Medical
applications and use of marijuana--a study by the Tennessee Department of
Public Health.
Sell SH.
Publication Types:
PMID: 6247570 [PubMed - indexed for MEDLINE]
|
53: NIDA Res Monogr. 1980;31:199-221. |
Marijuana
research findings: 1980. Therapeutic aspects.
Cohen S.
Publication Types:
·
Review
PMID: 6252470 [PubMed - indexed for MEDLINE]
|
54: Annu Rev Pharmacol
Toxicol. 1980;20:415-28. |
Advances
in ocular pharmacology.
Zimmerman TJ, Leader B, Kaufman HE.
Publication Types:
·
Review
PMID: 6155823 [PubMed - indexed for MEDLINE]
|
55: Annu Rev Pharmacol
Toxicol. 1980;20:151-72. |
Potential
therapeutic usefulness of marijuana.
Lemberger L.
Publication Types:
·
Review
PMID: 6104468 [PubMed - indexed for MEDLINE]
|
56: JAMA.
1979 Nov 2;242(18):1962. |
From
the NIH: Reports of marihuana for glaucoma treatment are misleading;
researchers will study.
[No authors listed]
PMID: 480632 [PubMed - indexed for MEDLINE]
|
57: Am Pharm. 1979 Sep;19(10):25-8. |
Marijuana
by prescription.
Tucker L.
Publication Types:
PMID: 539533 [PubMed - indexed for MEDLINE]
|
58: Ann Ophthalmol. 1979
Feb;11(2):203-5. |
Marihuana
in Ophthalmology-past, present and future.
Green K.
PMID: 434738 [PubMed - indexed for MEDLINE]
|
59: Am Med News. 1979 Jan
26;22(4):17-8. |
MDs,
hospitals debate issue as patients experiment with medical use of marihuana.
[No authors listed]
PMID: 10240357 [PubMed - indexed for MEDLINE]
|
60: J Psychedelic Drugs. 1979
Jan-Jun;11(1-2):135-44. |
On cannabis and health.
Zinberg NE.
PMID: 522164 [PubMed - indexed for MEDLINE]
|
61: JAMA.
1978 Oct 13;240(16):1761-3. |
Marijuana. Does it have a possible
therapeutic use?
Cohen S.
PMID: 691183 [PubMed - indexed for MEDLINE]
|
62: Ann Intern Med. 1978
Oct;89(4):539-49. |
Cannabis,
1977.
[No authors listed]
Recent advances in development of immunoassay methods for marijuana constituents
in body fluids provide a rapid means of detection for forensic purposes and a
useful research tool for accurate quantitation of dose-response relation.
Therapeutic possibilities of cannabis, such as reduction in intraocular
pressure and bronchodilatation, may stimulate development of synthetic
cannabinoid derivatives that meet acceptable standards of safety and effiicacy
for treatment of glaucoma and asthma. Cannabis use may have harmful short- and
long-term impacts on health. Potentially serious short-term effects include
predisposition to angina during exercise in patients with coronary artery
disease. Even in healthy subjects, marijuana smoking decreases peak exercise
performance, possibly because of its chronotropic effect with achievement of
maximum heart rate at reduced work loads. Although no conclusive evidence
exists for long-term biologic consequences of chronic cannabis use, preliminary
evidence, suggesting impairment in pulmonary function and immune responses,
requires further investigation with large-scale epidemiologic studies.
Publication Types:
·
Review
PMID: 358885 [PubMed - indexed for MEDLINE]
|
63: JAMA.
1978 Sep 29;240(14):1469-70. |
High
interest in medical uses of marijuana and synthetic analogues [new]
Montgomery BJ.
PMID: 682339 [PubMed - indexed for MEDLINE]
|
64: Naturwissenschaften. 1978 Apr;65(4):174-9. |
Toward
drugs derived from cannabis.
Mechoulam R, Carlini EA.
Recent work aimed at the introduction of natural and synthetic cannabinoids as
drugs is reviewed. Delta1-Tetrahydrocannabinol (delta1-THC) is mainly
investigated as a potential drug against glaucoma and asthma, and as an
antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the
clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are
currently being investigated as analgetics and as sedative-relaxants.
Publication Types:
·
Review
PMID: 351429 [PubMed - indexed for MEDLINE]
|
65: West Indian Med J. 1978
Mar;27(1):16-25. |
The
treatment of glaucoma using a non-psychoactive preparation of Cannabis sativa.
West ME, Lockhart AB.
PMID: 654244 [PubMed - indexed for MEDLINE]
|
66: NIDA Res Monogr. 1977
Jul;(14):194-225. |
Therapeutic aspects.
Cohen S.
Publication Types:
· Review
PMID: 411042 [PubMed - indexed for MEDLINE]
|
67: West Indian Med J. 1977
Jun;26(2):66-70. |
The
potential use of Cannabis sativa in ophthalmology.
Lockhart AB, West ME, Lowe HI.
PMID: 878455 [PubMed - indexed for MEDLINE]
|
68: Adv Drug Res. 1977;11:97-189. |
Potential
therapeutic agents derived from the cannabinoid nucleus.
Pars HG, Howes JF.
PIP: Drugs derived from Cannabis sativa (Cannabinceae) were used until the
1940's for their stimulant and depressant effects for treating somatic and
psychiatric illnesses. Renewed interest in marihuana research began in the
1970's and again pointed to the therapeutic potential of cannabinoids. Safer
and more useful therapeutic agents may be generated from cannabinoids similarly
to morphine, lysergic acid diethylamide, and cocaine which have structurally
related analgesics, oxytoxics, and local anesthetics respectively. It has been
shown that the C-ring in cannabinoids can be substituted with a variety of
nitrogen and sulfur-containing rings without loss of CNS (central nervous
system) activity. Cannabinoids have been shown to inhibit prostaglandin
synthesis, intensify pressor effects of endogenous amines like norepinephrine,
and enhance the stimulant effects of amphetamine. Cannabinoids' therapeutic
potential lies in the areas of analgesics and anticonvulsants, and for use as a
sedative-hypnotic, an antiglaucoma agent, an antiasthmatic agent, an
antidiarrheal agent, and possibly as an anticancer and immunosuppressant agent.
Publication Types:
·
Review
PMID: 24325 [PubMed - indexed for MEDLINE]
|
69: Ophthalmologica.
1976;172(2-3):122-7. |
[Action
of delta-9-tetrahydrocannabinol on ophthalmotonus]
[Article in French]
Cuendet JF, Shapiro D, Calanca A, Faggioni R, Ducrey N.
PMID: 1256748 [PubMed - indexed for MEDLINE]
|
70: Invest Ophthalmol. 1975
Apr;14(4):261-3. |
Marihuana
and the eye.
Green K.
PMID: 1123282 [PubMed - indexed for MEDLINE]
|
71: Invest Ophthalmol. 1975
Jan;14(1):52-5. |
Marijuana smoking and reduced pressure in
human eyes: drug action or epiphenomenon?
Flom MC, Adams AJ, Jones RT.
Normal pressure within the human eye was reduced after smoking a socially
relevant dose of marijuana (12 mg. delta9-9-tetrahydrocannabinol), but only for
light to moderate users who experienced a substantial "high" and a
state of peaceful relaxation from the experimental dose. Analysis suggests an
indirect effect of the drug associated with relaxation-a psychophysiologic
state that can be produced by drug and nondrug means.
Publication Types:
PMID: 1089090 [PubMed - indexed for MEDLINE]