A broader view on deriving a reference dose for THC the in foods

An Acute Reference Dose (ARfD) of 1 µg of delta-9-tetrahydrocannabinol (THC) per kilogram (kg) of body weight (bw) per day was recommended by the European Food Safety Authority (EFSA) for its assessment of possible acute health risks from the intake of industrial hemp food products. The scientific basis for this opinion, such as their choice of a Point of Departure for identification of the Lowest Observed Adverse Effect Level (LOAEL) for THC on the central nervous system, and the seeming absence of an experimental No Observed Adverse Effect Level (NOAEL), is critically reviewed. Moreover, the risk assessment for an ARfD derivation for THC is then reconsidered. In contrast to the EFSA Scientific Opinion of 2015, a higher LOAEL is presently identified from pharmacokinetic and pharmacodynamic studies, and forensic data, in representative cohorts of healthy humans after oral administrations of low THC doses. A NOAEL for THC is derived through this combination of results, demonstrating a threshold for impairment of psychomotor function only after intake of an oral THC bolus beyond 2.5 mg for the average healthy adult. This 2.5 mg dose produces mean THC blood serum levels of <2 ng/mL, as well as do two doses when taken daily within a time interval of ≥6 h. The forensic threshold of THC that is correlated with the impairment of psychomotor function is known to be between 2 and 5 ng/mL in blood serum for adults. For an appropriately spaced intake of 2 × 2.5 mg THC per day, an adult can therefore be regarded as being at the NOAEL. Applying a default uncertainty factor of 10 for intraspecies variability to a NOAEL of 2 × 2.5 mg (over ≥6 hours) for THC, yields a “daily dose of no concern” or a “tolerable upper intake level” of 0.50 mg, corresponding to 7 µg/kg bw. Starting with a NOAEL of only 2.5 mg, consumed as a single bolus, the lowest possible daily THC Acute Reference Dose would therefore be 0.25 mg, or 3.5 µg/kg bw for healthy adults, as the absolutely most conservative estimate. Other justifiable estimates have ranged up to 14 µg/kg bw per day.