Commentary on DEA Scheduling of Locasercin

The findings reported by the sponsor as presented by the DEA and FDA strongly support theconcern that Locacerin (Belviq) poses a strong risk of abuse, possible dependence and likely

diversion. Belviq has demonstrated physiologically relevant binding affinity data for the 5-

HT2A. Agonist effects at 5-HT2A receptors are known to mediate hallucinogenic properties ofdrugs with known abuse liability such as lysergic acid diethylamide (LSD). It is concerning

that the sponsor sought to minimize the concerns associated with 5-HT2A agonism by

suggesting that the differences in affinity/potency of lorcaserin for the two 5-HT receptorsubtypes represent a functional selectivity for 5-HT2C activity. However, as shown in the

FDA reviews, lorcaserin is a functional 5-HT2A agonist at clinically significant (nanomolar)

concentrations and concentrations that can clearly be obtained in the setting of intentional

abuse, drug interaction or even therapeutic use. Based on the known reported hallucinogen-like behavioral effects of lorcaserin reported in human trials, it is likely that the threshold for

5-HT2A agonist effects is indeed met at therapeutic doses.

Abuse studies comparing Belviq to other drugs of abuse such as ketamine that were

 performed by the sponsor also provided compelling evidence that lorcaserin is likely to beabused. The FDA review suggests that euphoria associated with Belviq is long-lasting,

corresponds with maximum Belviq plasma concentrations, and is accompanied by other

adverse events consistent with hallucinogen intoxication. The Controlled Substances Staff

also concluded that “the ability of lorcaserin to produce hallucinations, euphoria, and positivesubjective responses, in healthy individuals and in obese patients, at doses greater than the

 proposed therapeutic dose of 20 mg suggests that lorcaserin can produce psychic dependence

 similar to that of other 5-HT 2 agonist hallucinogens”. Based on these findings, a schedulingrecommendation of C-II may be more appropriate for lorcaserin. Because of the severe

abuse potential and strong effects on perception and cognition, hallucinogens are rightfully

associated with more stringent controls. It is therefore difficult to understand the C-IVrecommendation for lorcaserin based on comparisons that do not take mechanism of action

or drug class into consideration.

From a benefit risk perspective, Belviq produces modest weight loss at best and can also

cause cognitive changes, euphoria, and hallucinatory experiences at and above the

recommended dose. Based on these findings, Belviq should be placed into Schedule II of theCSA, which would prevent patients from receiving refills. Requiring patients to obtain a new

 prescription each time the medication is dispensed would promote closer oversight by the

 prescribing health professional and provide needed controls over the distribution of this product. In time, review of post-marketing experience will give regulators and physicians a

 better understanding of how Belviq®

will be used under real-world conditions. Prescription

drug abuse has already reached epidemic proportions; we should not contribute to this urgent public health threat by opening up widespread, lightly regulated access to a medication with

limited medical benefits and a clear risk of abuse.