Antiemetic Effect of Intramuscular Levonantradol in Patients Receiving Anticancer Chemotherapy

Abstract

Positive results of investigations of the antiemetic activity of delta‐9‐tetrahydrocannabinol (THC) in patients receiving cancer chemotherapy have led to the development of levonantradol, a synthetic derivative of THC. We assessed both the antiemetic activity and toxicity of intramuscular levonantradol in patients receiving cancer chemotherapy who were refractory to conventional antiemetic therapy. An open dose‐finding study was conducted using initial doses of 0.5 mg. Doses were escalated by 0.5 mg when an incomplete response with no toxicity was observed. Of the 28 patients initially treated, 25/28 (89 per cent) achieved a complete or partial antiemetic response at doses ranging from 0.5 to 1.5 mg. There was no difference in response rate with respect to age or patient size. Of the 31 patients evaluable for toxicity, six reported none. Dysphoria, the dose‐limiting toxicity, occurred in five patients (16 per cent) at 1.0 to 1.5‐mg doses. The most commonly reported side effects were somnolence (48 per cent) and dry mouth (32 per cent). We conclude that intramuscular levonantradol is an effective antiemetic at doses as low as 0.5 mg.

Gone to Pot – A Review of the Association between Cannabis and Psychosis

“…The use of these agents for the treatment of pain syndromes, chemotherapy-induced nausea, and spasticity in multiple sclerosis was followed by reports of transient psychotomimetic effects among patients. The psychotomimetic effects reported were similar to that with cannabis including “loss of control,” thought disturbances, feelings of unreality, apprehension, fear and paranoia, anxiety and panic, dissociation, depersonalization, dysphoria, difficulty concentrating, hallucinations, perceptual alterations, amnesia, and anxiety (48–62). These effects were dose-related and proportional to the affinity of the compound for the CB 1 R. The high incidence of intolerable behavioral side effects in fact, led to the discontinuation of drug development of levonantradol as an analgesic.…”

Therapeutic use ofCannabis sativaon chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis

“…• One study compared two cannabinoid drugs: Citron et al (1985). • Twenty studies were excluded because they were not the object of the present review (non-randomized, open-label, absence of comparison between cannabinoids and control drugs, correspondence, lack of relevant data, data on physiological measurements only): Ekert et al (1979), Colls (1980); Garb et al (1980); Lucas and Laszlo (1980); Rose (1980); Cronin et al (1981); Heim et al (1981); Levitt et al (1981); Sweet et al (1981); Cone et al (1982); Kenny and Wilkinson (1982); Lucraft and Palmer (1982); Niamatali et al (1984); Cunningham et al (1985Cunningham et al ( , 1988; Devine et al (1987); Niiranen and Mattson (1987); Vinciguerra et al (1988); Abrahamov et al (1995); Gilbert et al (1995).…”

Cannabis, Cannabinoids, and the Association with Psychosis

“…Patients being treated with these synthetic cannabinoids have reported to experience transient psychotic symptoms, such as "loss of control", thought disturbances, feelings of unreality, apprehension, fear and paranoia, anxiety and panic, dissociation, depersonalization, dysphoria, difficulty concentrating, hallucinations, perceptual alterations, amnesia and anxiety (Citron et al, 1985;Cronin et al, 1981;Diasio et al, 1981;Heim et al, 1984;Heim et al, 1981;Jain et al, 1981;Kenny and Wilkinson, 1982;Laszlo et al, 1981;Leweke et al, 1999;Sheidler et al, 1984;Stambaugh et al, 1984;Stuart-Harris et al, 1983;Volkow et al, 1991;Wesnes et al, 2009). Patients being treated with these synthetic cannabinoids have reported to experience transient psychotic symptoms, such as "loss of control", thought disturbances, feelings of unreality, apprehension, fear and paranoia, anxiety and panic, dissociation, depersonalization, dysphoria, difficulty concentrating, hallucinations, perceptual alterations, amnesia and anxiety (Citron et al, 1985;Cronin et al, 1981;Diasio et al, 1981;Heim et al, 1984;Heim et al, 1981;Jain et al, 1981;Kenny and Wilkinson, 1982;Laszlo et al, 1981;Leweke et al, 1999;Sheidler et al, 1984;Stambaugh et al, 1984;Stuart-Harris et al, 1983;Volkow et al, 1991;Wesnes et al, 2009).…”