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Treatment of Crohn's Disease with Cannabis: An Observational Study



The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. To describe the effects of cannabis use in patients suffering from CD. In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.
• August
Background: The marijuana plant cannabis is known to have
therapeutic effects, including improvement of inflammatory
processes. However, no report of patients using cannabis for
Crohn’s disease (CD) was ever published.
Objectives: To describe the effects of cannabis use in
patients suffering from CD.
Methods: In this retrospective observational study we
examined disease activity, use of medication, need for
surgery, and hospitalization before and after cannabis use in
30 patients (26 males) with CD. Disease activity was assessed
by the Harvey Bradshaw index for Crohn’s disease.
Results: Of the 30 patients 21 improved significantly after
treatment with cannabis. The average Harvey Bradshaw
index improved from 14 ± 6.7 to 7 ± 4.7 (
< 0.001). The need
for other medication was significantly reduced. Fifteen of the
patients had 19 surgeries during an average period of 9 years
before cannabis use, but only 2 required surgery during an
average period of 3 years of cannabis use.
Conclusions: This is the first report of cannabis use in Crohn’s
disease in humans. The results indicate that cannabis may
have a positive effect on disease activity, as reflected by
reduction in disease activity index and in the need for other
drugs and surgery. Prospective placebo-controlled studies
are warranted to fully evaluate the efficacy and side effects
of cannabis in CD.
2011; 13: 455–458
Crohn’s disease, inflammatory bowel disease, cannabis,
Treatment of Crohn’s Disease with Cannabis:
An Observational Study
Timna Naftali MD1, Lihi Bar Lev BA2, Doron Yablekovitz MD1, Elisabeth Half MD1 and Fred M. Konikoff MD1
1Institute of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba affiliated with Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
2Department of Psychology, Faculty of Social Sciences, Tel Aviv University, Ramat Aviv, Israel
The marijuana plant, Cannabis sativa, has been used
as a medicinal treatment for a variety of diseases [1].
Cannabinoids have been reported to alleviate neurological
conditions including multiple sclerosis-related symptoms such
as spasticity, pain, tremor and bladder dysfunction [2]. Other
neurological conditions, such as chronic intractable pain, dys-
tonic movement disorders, and Tourettes syndrome were also
reported to be alleviated by cannabis use [3]. Cannabis has
been used to treat anorexia in AIDS and cancer patients [2,3].
In gastroenterology, cannabis has been used to treat anorexia,
emesis, abdominal pain, gastroenteritis, diarrhea, intestinal
inammation, and diabetic gastroparesis [4].
e cannabis plant contains over 60 dierent compounds,
which are collectively referred to as cannabinoids [5]; of them
Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
seem to be the most active. Cannabinoids have a profound
anti-inammatory eect, mainly through the CB2 receptor
[2]. Cell-mediated immunity was found to be impaired in
chronic marijuana users [6]. A potent anti-inammatory
eect of cannabis was observed in rodents [7]. Studying the
functional roles of the endocannabinoid system in immune
modulation reveals that it is involved in almost all major
immune events. Cannabinoids shi the balance of pro-
inammatory cytokines and anti-inammatory cytokines
towards the T helper cell type 2 proles (2 phenotype)
and suppress cell-mediated immunity, whereas humoral
immunity may be enhanced [8]. erefore, cannabinoids
may be used to treat various inammatory conditions
including rheumatoid arthritis. In a mouse model of colitis,
cannabinoids were found to ameliorate inammation [9].
Consequently, the non-conventional medical community
has recommended cannabis for patients with inammatory
bowel disease. However, there are no systematic reports of
the eects of cannabis on IBD. e aim of this study was to
describe the response of patients with Crohns disease who
have used cannabis to ameliorate their symptoms.
is was a retrospective observational study. A voluntary
organization that distributes cannabis for legally authorized
medical use in Israel was contacted. We interviewed patients
with CD who had permission from the Ministry of Health to
receive cannabis for their symptoms. Patients were questioned
about the details of their disease, previous medical and surgi-
cal treatments, and the reason for using cannabis. Disease
activity before and aer cannabis use was estimated by the
Harvey Bradshaw index. All patients assessed their general
IBD = inflammatory bowel disease
CD = Crohn’s disease
• August
well-being before and aer cannabis use on a Visual Analog
Scale. e scale ranged from 0, which represented “very poor
general well-being” to 10, indicating “excellent well-being.
Whenever possible, medical documents were reviewed for
objective signs of disease severity, such as number of hospital
admissions and use of other drugs, particularly steroids. e
dose and form of administration of cannabis were docu-
mented. e study was approved by the institutional ethics
committee of our hospital.
irty patients with CD who were using cannabis were inter-
viewed. e average age was 36 years (range 21–65 years)
and four were female. One patient with CD had a history
of partial pancreatectomy for serous cystadenoma, one had
asthma and two had hypertension. All other patients were
generally healthy apart from their CD. Before the use of
cannabis, ve patients had undergone right hemicolectomy,
three had resection of the terminal ileum, two had resection
of a proximal section of the ileum, and three had drainage
of a perianal stula. One patient with severe colitis had a
total proctocolectomy with ileoanal anastomosis. Aer the
operation she developed perianal disease and the diagnosis
was changed from ulcerative colitis to Crohns disease. Of the
15 patients who had an operation before using cannabis, 2
(13%) required another surgery during an average time of 2
years while on cannabis. e average duration of disease was
11.3 years (range 1–41 years). Twenty patients with CD had
inammation of the terminal ileum, 5 had inammation of
the more proximal ileum and 8 had Crohn’s disease of the
colon. One patient had pouchitis. Crohn’s disease was stuliz-
ing in 10 patients, brostenotic in 5, and luminal in 15. Before
cannabis use, 27 patients had received 5-ASA (5-aminosali-
cylic acid), 26 received corticosteroids, 20 took thiopurines,
6 took methotrexate, and 12 took anti-tumor necrosis factor
antibodies. Of 30 patients, 16 smoked tobacco regularly, 3
smoked tobacco before using cannabis but stopped when
they started cannabis use, and 14 never smoked tobacco. Of
the three patients who stopped tobacco smoking, one did not
improve (Harvey Bradshaw score of 4 both before and aer
cannabis use), one improved signicantly (from 11 to 2), and
one improved slightly (from 9 to 7), Although tobacco smok-
ing is known to have a negative eect on Crohn’s disease,
these results do not indicate that smoking cessation in itself
had any eect on disease severity in our patients.
e indication for cannabis use was lack of response to
conventional treatment in 21 patients and chronic intractable
pain in 6. Another four patients smoked cannabis for recre-
ation and continued as they observed an improvement in their
medical condition. Most patients smoked cannabis in the form
of hand-rolled cigarettes (“joints”). Four patients inhaled the
smoke through water (“bong”), and one patient preferred to
consume it orally. Most smoked between one and three “joints
a day, but one patient with chronic pain smoked seven joints a
day. Since one cigarette contains about 0.5 mg of THC, patients
were using 0.5–1.5 mg/day THC, with the exception of one
patient who was using 3.5 mg. e average duration of can-
nabis use was 2.14 years (range 3 months to 9 years). In 14
patients the duration of cannabis use was less than a year.
All patients stated that consuming cannabis had a positive
eect on their disease activity. is is also reected in the
Visual Analog Scale, which increased from 3.1 to 7.3. e
Harvey Bradshaw index decreased from 14 ± 6.7 to 7 ± 4.7
(P < 0.001) [Figure 1]. e mean number of bowel move-
ments decreased from eight to ve a day and the need for
other drugs was signicantly reduced [Table 1]. Of particular
interest is the observation that cannabis may have a steroid-
sparing eect, since the number of patients requiring steroid
treatment was reduced from 26 to 4. Fieen of the patients
had 19 surgeries during an average period of 9 years before
cannabis use, but only 2 required surgery during an aver-
age period of 3 years of cannabis use. In nine patients can-
nabis treatment did not induce a signicant improvement,
as reected by a change of less than 4 points in the Harvey
Bradshaw index. ree of these patients did not respond to
THC = Δ9-tetrahydrocannabinol
Average Range
Age (yrs) 36 2165
Male/Female 26/4
Disease duration (yrs) 11.3 141
Disease phenotype 15 luminal, 10 fistulizing, 5 fibrostenotic
Duration of cannabis
2.1 yrs 3 mos–9 yrs
Amount consumed
2.4 0.57
Joint = cigarette
Table 1. Patient characteristics
Figure 1. Harvey Bradshow index before and after cannabis use
1 11 13 15 17 19 21 23 25 27 293 5 7 9
Before cannabis
After cannabis
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the ecacy of cannabis in Crohn’s disease. e restraint from
the use of an illegal drug may have played a role.
e observed benecial eect in this study may be due to
the anti-inammatory properties of cannabis, but additional
eects of cannabinoids may also play a role. Cannabinoids
inuence gastrointestinal motility and, in particular, have an
anti-diarrheal eect, as observed in mice injected with chol-
era toxin [12]. e central eect of cannabinoids may induce
a sensation of general well-being, which could contribute to
the feeling that cannabis use is benecial. However, this gen-
eral eect wears o with time as tolerance develops, while the
positive eect of cannabis on disease activity in our patients
was maintained for an average period of 3.1 years.
One of the reasons that cannabis is unappealing to many
patients is that it is administered by smoking. Smoking in
general is unacceptable to both medical professionals and
many patients. e negative eect of tobacco smoking on
Crohn’s disease is also well known. Several studies demon-
strated a dose-related adverse eect of cannabis on large
airway function, but not on small airway function, which is
compromised by tobacco smoking [13,14]. Smoking cannabis
is the preferred mode of consumption because upon smok-
ing, blood levels of cannabinoids rise rapidly and a central
eect is achieved quickly. However, an anti-inammatory
eect, especially in the gut, may be achieved equally well by
consuming cannabis orally.
Although many side eects were connected with cannabis
use, most of them were in people who consumed other drugs
and alcohol together with cannabis. When consumed alone,
the safety prole of cannabis is very good [15]. Wang et al.
[16] reviewed 31 studies of medical cannabis use and found
that 96% of 4779 adverse events were minor. e relative risk
for serious adverse events was 1.04, which was not dierent
between the placebo and study groups. Cannabinoids may
therefore be a potential addition to the currently limited
arsenal of medications used to treat IBD. On the other hand,
because the use of medical cannabis may be exploited by
drug abusers, extra caution is necessary before cannabis can
be recommended to patients. A placebo-controlled study is
needed to fully investigate the therapeutic value of cannabis
for the treatment of Crohns disease.
e authors would like to thank the Tikun Olam organization for
their help in conducting the study.
Corresponding author:
Dr. T. Naftali
Institute of Gastroenterology and Hepatology, Meir Medical Center, Kfar Saba
44281, Israel
Phone: (972-9) 747-1045
Fax: (972-9) 744-1731
any other medical therapy, including TNF antagonists, and
are now awaiting surgery.
In this study, we describe 30 patients with CD for whom the
use of cannabis ameliorated disease activity and reduced the
need for other conventional medications. is is the largest
and, to the best of our knowledge, the rst reported series
of CD patients treated with cannabis. It is a retrospective
observational study and as such is not a replacement for a
prospective placebo-controlled study. ere may be a popula-
tion bias in the sense that some people may be more attracted
to the possibility of smoking cannabis than others. is may
explain the over-representation of young males in our study
population. Also, there may be patients who tried cannabis
and whose condition did not improve; they would be lost to
follow-up and are not represented in our study. However, the
benet reported by most of the patients in our study suggests
a possible signicant therapeutic potential. Due to the retro-
spective nature of our study there may be a bias in recalling
disease activity. However, several facts point to an objective
benet of cannabis use. e observed reduced use of steroids
(from 26 to 4 patients) [Table 2] and other drugs may point
to an objective benecial eect of cannabis. Whereas 25%
to 38% of operated Crohn’s disease patients are expected to
require a second operation within 5 years of the rst [11],
only 2 of 15 patients (13%) who had surgery before cannabis
consumption required surgery while consuming cannabis.
Larger numbers and longer follow-up are needed to verify
whether use of cannabis reduces the need for surgery.
e eects of cannabinoids on the immune system are
diverse and include modulating proliferation of B cells, T cells,
and natural killer cells, modulating production of antibodies
and cytokines, and regulating functions of NK cells, mac-
rophages, T helper cells, mast cells and dendritic cells [10].
Although anti-inammatory eects of cannabis have been
described previously, there are no systematic descriptions of
TNF = tumor necrosis factor
NK = natural killer
Drug Before After
No treatment None 9
5-ASA 27 5
Corticosteroids 26 4
Thiopurine 20 10
Methotrexate 6 0
TNF antagonist 12 4
5-ASA = 5-aminosalicylic acid
Table 2. Medical treatment before and after cannabis use (n=30)
• August
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Many autoimmune diseases, including multiple sclerosis
(MS), are more prevalent in women. This, coupled with
prior findings implicating a role for the estrogen receptor
(ER) in MS, prompted Saijo et al. to uncover the underlying
molecular mechanisms. After determining that microglia,
resident myeloid cells in the brain, primarily express ERβ,
the authors showed that depending on the ligand, signaling
through ERβ could either induce or inhibit pro-inflammatory
gene expression. 17β-estradiol, which is more prevalent
in women, drove expression of pro-inflammatory genes,
whereas 5-androsten-3β,17β-diol (ADIOL) inhibited them.
This occurred because ADIOL, but not 17β-estradiol, led
to the recruitment of CtBP corepressor complexes, which
functioned with ERβ and the transcription factor AP-1 to shut
down pro-inflammatory gene expression. In women, this
pathway may be antagonized because of increased amounts
of 17β-estradiol, which competes with ADIOL for binding to
ERβ and does not induce the recruitment of CtBP. Synthetic
ligands that signaled similarly to ADIOL were protective
and therapeutic in a mouse model of MS, which suggests
that this pathway may be a useful target for therapeutic
2011; 13: 584
Eitan Israeli
Estrogen receptor's two faces
The immune system is constantly surveying the body for
signs of infection, but how can it distinguish viruses from
self? Viruses can be distinguished from self because their
nucleic acids contain specific characteristics, such as the
triphosphorylated RNA (PPP-RNA), that are not found in the
nucleic acids of host cells. The molecules that recognize
these viral structures, however, are still being identified.
Pichlmair and co-authors carried out a screen to identify
proteins that interact with PPP-RNA and identified several
members of the IFIT family of interferon-stimulated proteins.
In response to antiviral interferons, IFIT proteins formed
a molecular complex with other family members and RNA-
binding proteins. Subsequent biochemical and genetic
analysis focused on IFIT1 and found that, although it did not
appear to be involved in the initial detection of the virus, it
was highly induced in response to antiviral interferons and
was required for keeping viral growth in check in cultured
cells and in mice infected with vesicular stomatitis virus.
Although IFITs have been previously associated with inhi-
bition of protein translation, the authors presented data
consistent with IFIT1 functioning by sequestering viral nucleic
acids within the cell.
Nat Immunol
2011; 12: 10.1038/ni.2048
Eitan Israeli
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“Experience is not what happens to a man; it is what a man does with what happens to him”
Aldous Huxley (1894-1963), British novelist, most famous for his classic
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Diabetes Mellitus is one of the deadliest diseases in the world, while the current medications against this disease like acarbose represent many side effects such as diarrhea and abdominal discomfort. Many studies based on natural plants used in traditional medicine were performed to find or invent new drugs to treat diabetes mellitus disease. The traditional drug design based on the synthesis and analysis of compounds wanted to study expenses a lot of time and the cost of the synthesis process, while we can resolve these problems by using computational methods that help us to predict the efficacity, stability, and pharmacokinetics properties as a main step in the drugs design chain. In this study, the virtual screening was performed on a set of 49 compounds extracted from cannabis plants by using molecular docking simulation to examine their ability to create a stable complex with the alpha-amylase inhibitor which reduces blood glucose levels in the human body. Acarbose, a widely used anti-alpha amylase activity, was employed as a reference medicine. Further, the selected compounds which showed good binding affinity were subjected to the ADMET screening to predict the pharmacokinetics properties, Additionally, molecular dynamics testing was done to confirm the outcomes. The result was that 50 compounds docked in the binding site of the alpha-amylase protein, and 25 of those compounds demonstrated the ability to create a stable complex with the target. While the ADMET analysis indicated that two substances amongst would have favorable oral bioavailability and pharmacokinetics characteristics.
... One of the first studies showing improvement with cannabis was performed in Israel. This was an observational study in a small population of patients with CD, of whom 21 out of 30 patients reported an improvement in their condition as measured by the Harvey-Bradshaw Index for disease activity [24]. Although no placebo control group was present in the study, it opened the door for other clinical studies regarding the potential benefits of medical cannabis in IBD patients. ...
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Inflammatory bowel disease (IBD) is an immune-mediated condition associated with chronic gastrointestinal (GI) inflammation requiring long term anti-inflammatory treatment in most patients. Unfortunately, despite the expanding IBD treatment toolbox, some patients are left with persistent symptoms including abdominal pain, nausea, reduced appetite, and diarrhea. The subsequent decline in quality of life often prompts patients to investigate complementary and alternative treatment options including cannabis to improve symptoms and quality of life. Cannabis is composed of thousands of compounds called phytocannabinoids, the most well known being delta-9-tetrahydrocannabinol and cannabidiol.¹ Cannabinoids bind to receptors, cannabinoid receptors 1 and 2, to produce the clinical effects described with medicinal and recreational cannabis use. The biochemical and functional evidence of the modulatory properties of cannabis on GI inflammation supports the need for more robust clinical studies to identify further therapeutic applications. Currently available cannabis studies lack consistent evaluation of primary endpoints, limiting the generalizability of findings. Therefore, formal, scientifically rigorous studies examining cannabis are needed to optimize confidence in our understanding of the clinical effects of cannabis.
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Cannabis, commonly known as marijuana, is a drug extracted from the Cannabis plant known for its psychotropic and medicinal properties. It has been used for healing purposes during ancient times, although its psychoactive components led to its restricted use in medicine. Nonetheless, cannabis is found to have modulatory effects on the endocannabinoid system exhibiting its medicinal role in the gastrointestinal (GI) system. Emerging animal and human studies demonstrate the influential effects of cannabis on a variety of GI diseases including inflammatory bowel disease, motility disorders and GI malignancies. It also has a regulatory role in GI symptoms including nausea and vomiting, anorexia, weight gain, abdominal pain, among others. However, both its acute and chronic use can lead to undesirable side effects such as dependency and addiction, cognitive impairment and cannabinoid hyperemesis syndrome. We will discuss the role of cannabis in the GI system as well as dosing strategies to help guide gastroenterologists to assess its efficacy and provide patient counseling before prescription of medical marijuana.
Multiple studies confirm use of Integrative Health (IH) therapies is common among children with IBD. Pediatric prevalence rates are compatible with or exceed IH use in adult IBD. Surveys indicate that biologically-based therapies are the most frequently utilized modality among the pediatric IBD population. Concurrent use of herbal remedies and dietary supplements (which we will define as biologically based IH therapies for the purpose of this chapter) and prescription medication is common and may cause untoward drug interactions. In this chapter, we review the available evidence for the safety and efficacy of the most commonly used biologically-based therapies and mind-body therapies in IBD. Clinicians need to know the prevalence of IH therapy utilization in the pediatric IBD population, parents’ receptivity towards these modalities as adjuvant therapies, and the reticence to disclose utilization. We suggest that maintenance of a cursory level of understanding and awareness of IH modalities, including knowledge of efficacy, interactions and contraindications, is essential to ensure patient safety.
Für den Begriff komplementäre und alternative Medizin (KAM) gibt es keine einheitliche Definition. Der Schwerpunkt der komplementären Verfahren liegt auf nichtpharmakologischen Therapieverfahren, die in einem Gesamtkonzept ergänzend zur Pharmakotherapie bei CED eingesetzt werden. Im deutschsprachigen Raum wird unterschieden zwischen komplementären Verfahren, die ergänzend zur konventionellen, sogenannten Schulmedizin eingesetzt werden, und alternativen Verfahren, die als Alternative zu den Standardverfahren eingesetzt werden. Alternative Verfahren sind vor diesem Hintergrund abzulehnen.
The effects of cannabis on lung function remain unclear and may be different from those of tobacco. We compared the associations between use of these substances and lung function in a population-based cohort (n = 1,037). Cannabis and tobacco use were reported at ages 18, 21, 26 and 32 yrs. Spirometry, plethysmography and carbon monoxide transfer factor were measured at 32 yrs. Associations between lung function and exposure to each substance were adjusted for exposure to the other substance. Cumulative cannabis use was associated with higher forced vital capacity, total lung capacity, functional residual capacity and residual volume. Cannabis was also associated with higher airway resistance but not with forced expiratory volume in 1 s, forced expiratory ratio or transfer factor. These findings were similar among those who did not smoke tobacco. In contrast, tobacco use was associated with lower forced expiratory volume in 1 s, lower forced expiratory ratio, lower transfer factor and higher static lung volumes, but not with airway resistance. Cannabis appears to have different effects on lung function from those of tobacco. Cannabis use was associated with higher lung volumes, suggesting hyperinflation and increased large-airways resistance, but there was little evidence for airflow obstruction or impairment of gas transfer.
Among 615 patients with Crohn's disease originally diagnosed at the Cleveland Clinic Foundation from 1966 to 1969, 592 have been followed (96%) for a mean of 13 yr. Of these, 438 had undergone operation. The purpose of this study was to determine how many of these patients had developed recurrences requiring another operation and to relate recurrences to the original anatomic location of disease (the clinical pattern) and surgical indication. Those patients with ileocolic disease had the highest recurrence: 53% compared with 45% for colonic and 44% for small intestinal patterns. Second recurrences were ileocolic pattern 35%, colon 34%, small intestine 38%. The estimated median time of recurrence was similar among these three groups. The presence of internal fistula or perianal disease as an indicator for surgery were associated with a higher likelihood of recurrence and a shortened estimated median time to recurrence. This study supports the concept of conservatism with regard to the management of these two complications for patients with Crohn's disease.
Many of the pharmacological effects of Δ9 THC can be antagonized in rodents by the administration of pemoline. These include effects on spontaneous activity, posture and the perception of noxious stimuli. Pemoline did not antagonize all of the effects of Δ9 THC.
Cannabis is the most widely used illicit drug in many developed societies. Its health and psychological effects are not well understood and remain the subject of much debate, with opinions on its risks polarised along the lines of proponents' views on what its legal status should be. An unfortunate consequence of this polarisation of opinion has been the absence of any consensus on what health information the medical profession should give to patients who are users or potential users of cannabis. There is conflicting evidence about many of the effects of cannabis use, so we summarise the evidence on the most probable adverse health and psychological consequences of acute and chronic use. This uncertainty, however, should not prevent medical practitioners from advising patients about the most likely ill-effects of their cannabis use. Here we make some suggestions about the advice doctors can give to patients who use, or are contemplating the use, of this drug.
Cannabis has a potential for clinical use often obscured by unreliable and purely anecdotal reports. The most important natural cannabinoid is the psychoactive tetrahydrocannabinol (Δ9-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 ofTHC. 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.
This review highlights the pharmacology, pharmacokinetics, pharmacological actions, therapeutic uses and adverse effects of cannabinoids. The effect of cannabinoids on anaesthesia is mentioned briefly. Important advances have taken place in cannabinoid research over the last few years and have led to the discovery of novel ligands. The possible clinical applications of these ligands and the direction of future research are discussed.
Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.
Cholera toxin (CT) is the most recognizable enterotoxin causing secretory diarrhea, a major cause of infant morbidity and mortality throughout the world. In this study, we investigated the role of the endogenous cannabinoid system (i.e., the cannabinoid receptors and their endogenous ligands) in CT-induced fluid accumulation in the mouse small intestine. Fluid accumulation was evaluated by enteropooling; endocannabinoid levels were measured by isotope-dilution gas chromatography mass spectrometry; CB(1) receptors were localized by immunohistochemistry and their messenger RNA (mRNA) levels were quantified by reverse-transcription polymerase chain reaction (PCR). Oral administration of CT to mice resulted in an increase in fluid accumulation in the small intestine and in increased levels of the endogenous cannabinoid, anandamide, and increased expression of the cannabinoid CB(1) receptor mRNA. The cannabinoid receptor agonist CP55,940 and the selective cannabinoid CB(1) receptor agonist arachidonoyl-chloro-ethanolamide inhibited CT-induced fluid accumulation, and this effect was counteracted by the CB(1) receptor antagonist SR141716A, but not by the CB(2) receptor antagonist SR144528. SR141716A, per se, but not the vanilloid VR1 receptor antagonist capsazepine, enhanced fluid accumulation induced by CT, whereas the selective inhibitor of anandamide cellular uptake, VDM11, prevented CT-induced fluid accumulation. These results indicate that CT, along with enhanced intestinal secretion, causes overstimulation of endocannabinoid signaling with an antisecretory role in the small intestine.