World Health Organization His Excelleney Tdme 12 Mr Anténio Guteres Faire MIR Secretary-General ofthe United Nations ot New York, NY 10017 Inca ese Usa, weer ECD 23 july 2018, ‘Dear Me Secretary-General, ‘The fortieth meeting oF the WHO Expert Committee on Drug Dependence (ECDD) ‘convened from 4 to 7 June 2018 at WHO headquarters in Geneva, The fortieth ECDD meeting “was dedicated tothe review of cannabis an its component substances, CCND Resolution 52/5 noted tht the health effects of cannabis had not been recently reviewed and requested the WHO ECDD to provide an updated report. The thirty-cighth ECD \(November,2016) reviewed updates presented by the Secretariat and recognised an increase in ‘the use of cannabis and its eomponeats for medical purposes and the emergence of new ‘cannabis-eated pharmaceutial preparations for therapeutic use. The Committee further ‘recognised that cannabis had never teen subject toa formal eview and therefore recommended that pre-eviews of cannabis an its component substances be evaluated a a specifie ECDD ‘meeting dedicated to those substances, Following those recommendations, the fortieth ECDD undertook a eiial review of cannabidiol (CBD). Italso carted cat pre-reviews of cannabis plant and resin; extracts and tinctures of cannabis; delts-9-etrahysrocannabinol (THC); and isomers of THC. ‘With reference to Article 3, paragraphs | and 3 of the Single Convention on Narcotic Drugs (1961), a amended by the 1972 Protocol, | am pleased to submit the recommendations of the fortieth ECDD as follows: Cannabiatol (CBD) ‘The Committee recommended that preparations considered tobe pure CBD should not be scheduled within the Intematicnal Drug Control Conventions, ENCL: (1) cc: MsJ. Dedeyre-Amann, Chief Secretariat to the Governing Bodies, UNODC Tabi Seal a - HATER ‘raaisation mondial del Santé + Bomgnanopramsai apatcoarsis + Onaizacisn Mundial dla SaatHis Excellency, Mr Anténo Guterres Page? Sexrery-Genal ofthe Unite Nason, New York Cannabis plant and resin ‘The Committe concluded that theres sulficient evidence to proceed toa Critical Review Extracts and tinctures of cannabis ‘The Committe concluded that there is sufficient evidence to proceed toa Critical Review Delta-9-THC ‘The Committe concluded that there is sufficient evidence to proceed toa Critical Review Isomers of THC ‘The Committee concluded that there i sufficient evidence to proceed toa Critical Review ‘The recommendations and the assessments and findings on which they are based are set cut in detail in the WHO Expert Committee on Drug Dependence Forteth report. An extract of ‘the report i attached in Annex 1 ofthis Teter. | would like to take this opportunity to inform you thatthe forty-frst meeting ofthe ECDD will tke place in November 2018. At tha time, the Committe will undertake critical reviews of the above-mentioned cannabis components (cannabis plant and resin; extracts and tinctures of| «cannabis; Delta9-THC; Isomers of THC) as well as ofa number of New Psychoactive ‘Substances (NPS), including fentany/-analogues and other psychouctive substances. ‘Lam very pleased with the ongoing collaboration between WHO, the United Nations Office on Drugs and Crime (UNODC) andthe International Necoties Control Board (INCB), in particular, ow this collaboration has supported the work of the WHO Expert Committe on, rug Dependence, and more generally, the implementation of the operational recommendations ofthe United Nations General Assembly Special Sesion (UNGASS) 2016, wilh wy verry ber Ysa Perrone ‘tg. ‘Dr Tedros Adhanoln Ghebreyesus ‘Director-GeneralWorld Health Organization next Annex l- Extract from the WHO Expert Committee on Drug Dependence: Forteth report, ‘Cannabidiol (CBD) CCannabidiol is one ofthe naturally occursing cannabinoids found in cannabis plants “There are no case reports of abuse or dependence relating tothe use of pure CBD. No public health problems have been asiocisted with CBD use. (CBD har been found tobe goneraly well tolerated with a good safety profile. Adverse effects of CBD use include loss of appt, diathoea, and fatigue “Therapeutic aplications of CBD are being researched fora varity of clinical uses. Research in this area is most advanced inthe treatment of epilepsy. In clinica trials, one pure CBD product has demonstrated effectiveness for treating some forms of epilepsy such as Lennox-Castaut Syndrome and Dravet Syndrome that are often resistant to other forms of medication. Since the Committee met, a pure CBD produc has recived marketing appeoval by the US Food and Drug ‘Administration (FDA), ‘Cannabidiol (CBD) isnot specifically listed in the schedules of the 1961, 1971 or 1988 United [Nations Intemational Drag Control Conventions. However, if prepared aban extractor tincture of eannabis itis controlled in Schedule I ofthe 1961 Single Convention on Natcotie Drugs ‘There is no evidence that CBD asa substance is liable to similar abuse and similar ill-effets as substances inthe 1961 or 1971 Conventions such as cannabis or THC, respectively ‘The Committe recommended that preparations considered tobe pure CBD should not be scheduled, ‘Cannabis plant and resin ‘Cannabis is defined asthe lowering tops or separsted resin ofthe Cannabis sativa pnt. ‘Cannabis contains 121 reported phytocannabinoids, with the most prominent ofthese ‘compounds being A9-THC (THC) and cannabidiol (CBD). THC is thought tobe te principal itoxicant constituent of cannabis, ‘When consumed acutely, cannabis causes adverse effects such as dizziness and impaired motor contrl and cognitive function. Cannabis ean cause diving impairment. There are particular reported risks for children such as respiratory depression, tachycardia, and coma. The adverse effects of cannabis consumption ae similar to those produced by THC alone. Most ofthe adverse effects asocited with cannehis result from chronic use. Regular cannabis seis asociated with increased risk of mental health disorders suchas anxiety, depression, and psychotic illness. Chronic regular cannabis use i particularly problematic for young people as & ‘esult ofthe effets on the developing bran,World Health Organization snes Cannabis can cause physical dependence in humans as evidenced by the onset of cannabis ‘Withdrawal symptoms upon abstinence. Withdrawal syndromes inclode mood changes, instability, and sleep impairment. Clinical diagnostic guidelines such as DSM-5 and ICD-10 recognise cannabis use disorder, ‘The Committe considered information regarding the therapeutic indications of cannabis and ‘ongoing research for its possible medical eppications. Several counties permit the wse of| cannabis forthe teatment of medical conditions such as back pain, sleep disorders, depression, injury pain, and multiple sclerosis. Research with cannabis for its poteial medical ‘pplication is ongoing. ‘Cannabis plant and cannabis resin ae placed in Schedule I and Schedule IV of the 1961 Single Convention on Narcotic Drugs. Substances that are included in bath Schedules [and IV ofthe 1961 Convention on Narctie Drugs are particularly ible to abuse and to produce il-ffets, ‘Other substances included in both Schedules [and IV are fentanyl analogues and other opioids ‘considered especially dangerous. ‘The evidence presented tothe Committe di not indicate that cannabis plant and cannabis resin Were liable to produce illeffecs similar o these other substances that ae in Schedule IV ofthe 1961 Convention on Narcotic Drags. Te inclusion of cannabis and cannabis resin in Schedule IV may not appear to be consistent with the extra for Schedule IV. ‘The Committe conclude that thet is sufficient evidence to proceed to erica review of cannabis plant and cannabis resin ata future ECDD meeting and explore furher the appropriateness of ther current scheduling within the 1961 Convention, Extracts and tinctures of cannabis Extracts and tinctures of cannabis ate substances that have been extracted from the Cannabis sativa plant. These include preparations such a cannabis oils, teas, and nabiximols (an exact with approximately equal quantities of THC and cannabidiol). These substazces can be administered through various routes including through oal consumption anc smoke inhalation. Evidence around the dependence potential of extracts and tinctures of cannabis varies by substance. Tere ae no published studies that have evaluated the dependence potential of abiximols, but thee is limited evidence ofa withdrawal syndrome upon abzupt cessation (e.g. sleep disruption, mood changes. Te frequent use of butane hash oil has been associated with ‘physical dependence. The psychoactive constituent A9-THC present ina majority of extract has ‘been separately examined and has been shown to have dependence potent ‘There are few published studies that have evaluated the abuse potential of cannabis extracts in snimals or humans. There are, however, studies that have investigated the abuse potential of various components of extrects and tinctures of cannabis. Whilst particular components, suchas A9-THC, have demonstrated abuse potential, other components in these preparations, such a5, (CBD, do not have abuse potentialWorld Heaith Organization ‘na es Goer Tc TFL AT ‘The Commitee recognised thatthe tee: extracts and tinctures" as cited inthe 1961 Single ‘Convention on Narcotic Drugs encompasses preparations that have psychoactive properties as Wel as those tht donot have such properties. The Committe also recognised tha the psychoactive properties of these prepactions are due to-A9-THC and possibly isomers of THC, Substances which ae curently scheduled inthe 1971 Convention on Psychotropie Substances ‘Amongst the substances tht are not psychoactive within the preparations that are derived as extracts or tinctures of cannabis, some [ke cannabidiol have promising therapeutie indications, Cannabis extracts and tinctures ae placd in Schedule [ofthe 1961 Single Convention on Narcotic Drugs “The Committee noted thatthe category ‘extract and tinctures of cannabis’ encompasses a variety of very diverse formulations with varying ratios of cannabis components, in particular THC, and th or without psychoactive properties. ‘The Committe therefore concluded tha thee is suficent information to progress extracts and tinctures of eannabis to critical review at a future ECDD meeting in order to adress the necessity of continuing to include the nomenclature “extracts tnd ineures of cannabis” i the 1961 Convention. Delta-9-tetrahydrocannabinol (THC) ett-9-tetrahydrocannabinol (THC) re‘rs to four stereoisomers of A9-THC. One ofthese stereoisomers is known by the International Nonproprietary Name (INN), dronabinol, and has recognised therapeutic uses. (Chronic administration of A9-THC can induce physical dependence in laboratory animals and in ‘humans. This has been evidenced by the presence of withdrawal effects in animals and hua, subjects ‘The subjective effects of A9-THC wher administered orally resemble those of cannabis. However, there is itl evidence that onl A9-THC is used for non-medical purposes $0 as to ‘case a public health problem, A9-THC (dronabinol) has approval in a number of counties for therapeutic indications including anorexia associated with weight loss in patients with Acquired Immune Deficiency Syndrome (AIDS) and for nausea and vomiting astociated with eancer chemotherapy. A9-TH (dronabinol) is routinely administered orally ‘A9-THC and its stereoisomers are iste in Schedule I of the Convention on Psychotropic Substances of 1971 In previous ECDD reviews, A9-THC and especially dronabinol had been considered in & synthetic form as a pharmaceutical preraation,World Health Organization Annex ‘cna Goa berenneTcn ETP ATT WWE However, the Committee recognised that A9-THC, in particular, its active and naturally ‘occuring stereoisomer, dronabnol,tody also refers to the main psychoactive component of ‘cannabis and cannabis-derived psychoactive products. In this form, dronabinol produces similar ileffects, dependence, and abuse potential to cannabis which is placed under the 1961 Single Convention, A substance liable to similar abuse and productive of similar il-ffects as that of substance already scheduled within the 1961 Convention would normally be scheduled inthe same way a that substance. The Committee conclu that ther is sufficient information to progress A9-THC to critical review ata future ECDD meeting in order to adress the appropriateness ofits placement within the Conventions Isomers of THC “There are curetly six isomers of tetrahydrocannabinol (THC) listed in Schedule ofthe 1971 Convention, Of the six THC isomers reviewed here, the abuse potential of only two of these isomers: AB- ‘THC and A6a,10a-THC- have been evaluated in afew human sues. These studies found th the acute intoxicating effects ofthese substances are similar to those of A9-THC, but they are less potent. “There are no reports that THC isomers induce physial dependence. There are no reported ‘medical or veterinary uses ofthese isomers. ‘There is no evidence that any ofthese listed isomers are being abused o are likely tobe abused so sto constitute a public health or socal problem. However, the Committee noted the potetil Aificuly of differentiating between thse six isomers (listed in Schedule | ofthe 1971 Convention) from A9-THC (listed in Schedule Il ofthe 1971 Convention) sing standard ‘methods of chemical analysis due to their chemical similarities. The Committee further noted ‘tha this ls an important tector to consider in the scheduling ofthese isomers ‘The Committee conchided that there is sufficient information to progress the isomers of THC 10 critical review at a future ECDD meeting and to explore further the relevance oftheir current scheduling within the 971 Convention