Human Studies of Cannabinoids and Medicinal Cannabis 733major limiting factor in determining patients’ acceptance of cancer chemotherapy
(Carmichael1992).Premedicationwithanti-emeticsisroutine,butseverevomiting
induced by such drugs as cisplatin, dacarbazine or cyclophosphamide can be very
difficult to control.
The anti-emetic properties of cannabis were rediscovered in the 1960s, when
recreationalusersreceivingcancerchemotherapytoldtheirdoctorsitrelievedtheir
nausea. Anecdotal reports (e.g. Grinspoon and Bakalar 1993) preceded a range of
controlled clinical trials in the 1970s and 1980s. These established that natural
and synthetic forms of THC were invariably superior to placebo (Chang et al.
1979; Orr and Mckernan 1981; Jones et al. 1982). Controlled comparisons of THC
with the anti-emetics available at the time suggested that it is either equivalent
(Ungerleider et al. 1982) or superior (Formukong et al. 1989; Plasse et al. 1991; Orr
and Mckernan 1981; Einhorn et al. 1981; Niiranen and Mattson 1985; Dalzell et al.
1986;Niederleetal.1986;Pomeryetal.1986;Chanetal.1987;Pentaetal.1981;Levitt
1986) to such drugs as prochlorperazine, domperidone, alizapride, dexamethasone
and metoclopramide. Commonest unwanted effects included somnolence, dry
mouth, ataxia, dizziness, dysphoria, and postural hypotension. Oral THC and
nabilone often produced more unwanted effects than comparison drugs, yet THC
was usually preferred by patients (Ungerleider et al. 1982; Einhorn et al. 1981;
Niiranen and Mattson 1985; Dalzell et al. 1986).
Penta and colleagues (1981) reviewed 12 studies that examined the anti-emetic
effects of THC (9) or nabilone (3) involving 600 patients. They reported that
THC was “effective” in 8/9 and nabilone in 3/3. Levitt (1986) reviewed 55 stud-
ies, of which 32 were of randomised, double-blind design. Low-dose preventative
treatment gave better results than targeting established vomiting. Levonantradol
produced a higher frequency of dysphoric effects than nabilone or THC. A review
by Formukong et al. (1989) suggested that the emesis produced by certain drugs
(e.g. methotrexate, doxorubicin, cyclophosphamide, fluorouracil) responded bet-
ter to THC than others (e.g. nitrosoureas, mustine, cisplatin). Younger patients
responded better than older. Plasse and colleagues (1991) reviewed clinical expe-
rience with dronabinol (capsules of THC in sesame oil), which was first marketed
in the U.S. in 1987. Meta-analysis suggested that an optimal balance of efficacy and
unwanted effects is achieved with relatively modest doses of THC (i.e. 7 mg/m^2
or less). Sedation and psychotropic effects were commonly reported but were
usually only of mild to moderate intensity and resolved rapidly on discontinua-
tion.
Children seemed to respond well to nabilone (Dalzell et al. 1986; Chan et al.
1987) and to be tolerant of adverse effects, but confirmation is required. A small
pilot study (Abrahamov et al. 1995) indicated a positive response to∆^8 -THC in 8
children receiving highly emetic antineoplastic therapy for various blood cancers.
Vomiting was reported in 60% children receiving metoclopramide, but when∆^8 -
THCwasgivenorally2hbeforechemotherapyandrepeatedevery6hfor24h,
no vomiting occurred on any of the 480 occasions this strategy was applied. Two
children reported unwanted effects: both were “slightly irritable” and one (age 4)
showed “slight euphoria”. Surprisingly, this very promising result has not been
followedupwithamoredefinitivestudy.