On the duration of cannabis effects and the presence of THC in the body

When tetrahydrocannabinol (THC), the most important psychoactive ingredient in cannabis, is present in sufficiently high concentrations it affects brain function. It is important to know the duration of this effect, both for medical and recreational use. New studies indicate that small amounts of cannabis remain present in the brain longer than previously assumed and accumulate with repeated intake. The possible consequences are currently unknown. To guide information-based cannabis choices, we call for further research. Cannabis use is increasing [1], as are the average THC levels in cannabis products [2]. The question of the duration of THC presence in the brain and the subsequent effects thus become more urgent. Long-term negative effects have been suggested to involve cognitive impairment, including memory, learning and impulse control [3]. Some studies indicate that this may have to do with functional or structural changes in the brain [4, 5]. However, most psychoactive effects of THC fade during the first hours after cannabis smoking and are mostly gone 6–8 hours after intake [6]. After occasional smoking of 30–50 mg, a common intake per day for recreational users [7], THC plasma concentrations fall from approximately 50–100 ng/ml at peak to approximately 0.5–2 ng/ml at distribution equilibrium 6–8 hours later [8-10]. Twenty-four hours after smoking, most users will have plasma levels below 1 ng/ml and below the detection limit of several analytical methods (often 0.5 ng/ml). This could give the impression that THC is no longer present in the body. However, with an ultrasensitive analytical method, THC plasma levels have been detected for 10–28 days after smoking of approximately 30 mg THC on 2 consecutive days in an experimental study [11]. That study estimated the terminal half-life (T½) of THC in 10 subjects to be 4.3 (2.6–12.6) days. Recent population pharmacokinetic studies have reported a mean T½ of THC from 21.5 hours to 3.5 days [10, 12, 13]. According to general pharmacokinetic principles, the THC plasma concentration after a period of 5 T½ will be 3% of the level at distribution equilibrium. Taken together, these findings suggest that THC may be present in low concentrations from 5 to 60 days. An important question is whether these very low THC levels, which are comparable with the human plasma levels of the endocannabinoid anandamide [14], will be interfering with the brain function through an impact on the endocannabinoid systems. Repeated smoking within this period would lead to accumulated THC levels and probably increase the risk of interference. The duration of the low-concentration period shows marked individual differences in naturalistic studies of frequent smokers [15-18] and in less frequent cannabis smokers [19]. The reason for this variation in T½ is currently unknown, but could be dependent upon analytical methodology or biopharmacological factors such as gender, age, body mass index, pattern of use and drug interactions. In our opinion, data on the fate of THC in the human body expressed as comprehensive information on its T½, and similar to that required for medicinal drugs, should be available also to all users of cannabis. No external funding was necessary for this work. J.M. has acted as consultant for the Norwegian Ministry of Transportation and Communication and the police on concentration limits for drugs in drivers and as expert witness in Norwegian courts in cases on cannabis impairment. A.L.B.J. and J.G.B. have none to declare. Jørg Mørland: Conceptualization; writing-original draft; writing-review and editing. Anne Line Bretteville-Jensen: Writing-original draft; writing-review and editing. Jørgen G. Bramness: Writing-original draft; writing-review and editing.