ACMD advice 11 September 2018

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ACMD  
Advisory Council on the Misuse of Drugs 
 
Chair: Dr Owen Bowden-Jones 
Secretary: Zahi Sulaiman  
4th Floor (NE), Peel Building  
2 Marsham Street  
London, SW1P 4DF  
Tel: 020 7035 1121  
ACMD@homeoffice.gsi.gov.uk   
 
 
Rt. Hon. Sajid Javid MP 
Home Secretary 
2 Marsham Street  
London, SW1P 4DF  
 
Rt. Hon. Matt Hancock MP 
Secretary of State for Health and Social Care 
39 Victoria Street 
London, SW1H OEU 
 
11 September 2018  
 
Dear Home Secretary and Secretary of State for Health and Social Care, 
 
Re: Consultation on Cannabis-derived medicinal products  
 
Thank you (Home Secretary) for your letter of 26 July 2018, in which you accepted the 
Advisory Council on the Misuse of Drugs’ (ACMD’s) recommendations from our initial 
short-term review on Cannabis-derived medicinal products (CDMPs).  
 
On 15th August 201 8, further to the ACMD’s initial short -term review, the ACMD’s 
CDMP Working Group met with representatives of the Home Office, the Department 
of Health and Social Care (DHSC) and the Medicines and Healthcare products 
Regulatory Agency (MHRA) . This meeting considered the Government’s proposed 
interim approach for the rescheduling of  CDMPs, which included three components, 
designed to work together:  
 
• Component 1: An interim definition of a CDMP; 
• Component 2: Three access routes for prescribing CDMPs; and 
• Component 3: Guidance to support practitioners.  
 

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The ACMD is now providing advice on this interim approach, as well as a number of 
additional recommendations intended to strengthen the proposed approach. Given our 
conclusions and recommendations we believe it to be advisable to address our 
response to both of you.  
 
Component 1: Interim definition of CDMPs 
The ACMD reiterates its previous advice that CDMPs should meet defined safety and 
quality assurance standards to ensure that they do not put patients at risk of harm. As 
an interim measure, only products meeting these standards were recommended to be 
rescheduled to Schedule 2 of the Misuse of Drugs Regulations 2001. Any products 
not meeting these safety and quality assurance standards should remain in Schedule 
1. To achieve this, the formulation of a clear definition of a CDMP was recommended. 
 
The Government has now proposed an interim definition of a CDMP for medicinal use 
in humans, which includes the following three elements. 
 
1) It contains Cannabis, Cannabis resin, cannabinol or a cannabinol derivative. 
2) It is produced for medicinal use in humans. 
3) It is: 
i. a medicinal product; or  
ii. a substance or preparation for use as an ingredient of a medicinal 
product; or 
iii. a substance for use in the preparation or manufacture of an ingredient 
of a medicinal product.  
The ACMD has reviewed this definition and has reached the following conclusions.  
 
The interim definition does not include safety and quality assurance standards, as the 
ACMD previously recommended. Without explicitly setting these standards or referring 
to defined standards, it is impossible for prescribers to determine which products 
should be made available to patients as prescription medications. 
 
The ACMD concluded that element 1 of the interim definition, as currently drafted, is 
too broad. The ACMD is concerned that element 1 could potentially encompass a wide 
range of products not appropriate for medicinal use and these would be available to 
be prescribed with no information about their quality or safety. Examples include 
products of known acute harm, such as very high -tetrahydrocannabinol (THC) 
containing solid and edible products, liquid extracts, and products with impurities which 
have not undergone any quality control.   
 
Elements 2 and 3 lack clarity regarding the term ‘medicinal product’. Without further 
detail, elements 2 and 3 will not assist in identifying products specifically manufactured 
to an acceptable medicinal standard. 

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As is described in the Government’s interim proposal, prescribers will take sole 
responsibility for ensuring the safety, quality and efficacy of unlicensed CDMPs. 
However, the current lack of UK pharmacopoeial standards on CDMPs and the relative 
paucity of high quality clinical evidence at present means that on a practical level, 
prescribers will be unable to judge safety, quality and efficacy o f CDMPs when using 
the proposed CDMP definition.  This potentially puts patients at risk and is exactly the 
situation the ACMD expressed concern about in our letter of 19 July 2018.1  
 
In addition, the lack of a clear definition for CDMPs is regarded by the ACMD as a 
significant risk to their successful adoption and therapeutic use by clinicians and could 
lead to wider harms, including misuse and diversion.  
 
In view of these concerns, the ACMD recommends that the Home Office, DHSC and 
MHRA continue working on refining the definition of CDMPs to include appropriate 
standards so that only those products which meet those standards are available to be 
prescribed. The ACMD will further examine the definition in the longer-term review.  
 
Any definition of CDMPs should be underpinned by  existing regulations [The Misuse 
of Drugs Regulations 2001, The Human Medicines Regulations 2012, and The 
Controlled Drugs (Supervision and Management and Use) R egulations 2013] and 
clinical guidance specific to CDMP prescribing.  
 
Conclusion 1: The ACMD notes that th e proposed interim definition of a CDMP 
is currently extremely broad, with no reference to safety or quality. The lack of 
clarity in the definition s ignificantly increases the risk of unintended 
consequences.   
 
Recommendation 1: The Home Office, DHSC and MHRA to refine the definition 
of a CDMP as a priority.  
 
Component 2: Three access routes for prescribing CDMPs 
 
The ACMD previously recommended the development of additional frameworks and 
clinical guidance for ‘checks and balances’ to maintain safe prescribing of CDMPs to 
avoid harm to patients and others. The three access routes that shall enable CDMPs 
to be made available are:  
 
1. a ‘special’ unlicensed medicinal product that is for use in accordance with a 
prescription or direction of a specialist medical practitioner, or 
 
                                            
1 
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/727333/ACMD_advice_on_s
cheduling_of_cannabis_derived_medicinal_products.pdf  

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2. an investigational medicinal product without a marketing authorisation that 
is for use in a clinical trial, or 
 
3. a medicinal product with a marketing authorisation. 
 
The ACMD has reviewed and agreed the three proposed access routes by which a 
CDMP can be prescribed in the UK to ensure patient safety. 
 
Conclusion 2: The ACMD supports the availability of CDMPs by the three 
proposed access routes for prescribing to ensure patient safety.  
 
Designation order 
To enable the prescription of CDMPs by specified routes an d by specialist clinicians, 
CDMPs should be removed, a s part of their rescheduling, from the Misuse of Drugs 
(Designation) Order 2015.  
 
Recommendation 2: CDMPs meeting appropriate safety and quality standards 
under Schedule 2 should be exempted from the general designation of 
Cannabis, Cannabis resin, cannabinol and cannabinol derivatives under the 
Misuse of Drugs (Designation) Order 2015.  
 
Licence fees 
The ACMD agree s to the proposed amendment of the licence fees regulations to 
clarify the Secretary of State’s discretionary power to waive licence fees where 
appropriate.  
 
Component 3: Guidance to support practitioners 
 
The ACMD recommends that any g uidance to support practitioners in prescribing 
CDMP should address  both unlicensed products and those with marketing 
authorisation. In the proposal, the responsibility for prescribing an unlicensed CDMP 
falls within the existing framework for the prescription of unlicensed medications. The 
ACMD agrees that unlicensed CDMPs should be considered as a product of last resort 
and used only when no other drug with MHRA marketing authorisation meets the 
clinical need.  
 
Given the currently limited evidence base, and the unfamiliarity UK clinicians have with 
CDMPs, it is insufficient to make clinicians solely responsible for the safety , quality 
and efficacy of unlicensed ‘special’ CDMPs. In view of this , the ACMD supports the 
development of interim guidance by the DHSC and NHS-England (and its equivalents 
in Scotland, Wales and Northern Ireland ) for those prescribing CDMPs  (both 
unlicensed and those with MHRA marketing authorisation) . Guidance should be 
applicable to both public and private sectors . The ACMD anticipates that the interim 

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guidance will address the medical conditions for which CDMP should be used and will 
help prescribers to make appropriate clinical decisions around patient safety. 
 
The ACMD agrees with the involvement of the National Institute for Clinical Excellence 
(NICE) to develop substantial guidance to replace the interim guidance in due course. 
The substantial guidance should also address formulations, covering aspects such as 
high/low THC products, THC/ cannabidiol ( CBD) ratios and inhalable and edible 
products. 
 
Conclusion 3: The emphasis on the prescriber to ensure the safety, quality and 
efficacy of unlicensed ‘special’ CDMPs  means that clear interim guidance 
should be developed as a matter of urgency and be ready by the time of 
implementation to assist in clinical decision making.  
 
Recommendation 3: The DHSC and NHS  England (and their equivalents in 
Scotland, Wales and Northern Ireland ) to lead the development of interim 
guidance for clinicians considering prescribing a CDMP and pharmacists who 
will be required to source and dispense  CDMPs (including unlicensed ‘special 
medicinal products’  and products with MHRA marketing authorisation) . The 
ACMD supports the involvement of NICE in developing substantial guidance to 
replace the interim guidance in due course.  
 
Competency framework for prescribers  
 
The ACMD agree s with the proposed initial restriction of CDMP prescribing to 
clinicians on the specialist register of the General Med ical Council ( GMC) and 
suggests that this does not impede research on CDMPs from taking place. To prevent 
the prescribing of CDMPs outside clinicians’ specialist areas, the proposed restriction 
to clinicians on the specialist register should include the relevant specialist registration. 
Doctors authorised on study delegation log s should be considered as eligible to 
prescribe within their research setting.  
 
The ACMD stresses that a clear training pathway and competency framework should 
be developed to:  
 
• define safe, effective and ethical prescribing.  
• ensure the competence of prescribers of CDMPs. 
 
Recommendation 4: The DHSC (and its equivalent in Scotland, Wales and 
Northern Ireland) to develop, with stakeholders, a competency framework and 
training pathway for the prescribing of  CDMPs to support safe and effective 
prescribing.  
 
 

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Additional ACMD recommendations on interim proposals  
 
Content description  
 
Prescribers will need to know the content of a CDMP when making a clinical decision. 
The ACMD re-iterates that prescribers must have confidence in the composition and 
consistency of CDMPs to ensure patient safety . Labelling of CDMP s will support 
prescribers in clinical decision making and help to develop the clinical evidence base.   
 
Cannabis contains many different compounds, of which THC and CBD have been the 
most studied .2,3,4 The understanding of the precise therapeutic  action of THC and 
CBD, acting independently or together, is still developing. 5,6,7,8,9,10,11,12,13 Other 
compounds commonly present in Cannabis may potentiate or attenuate the clinical 
effects of THC and CBD. As a minimum, the actual amounts of THC and CBD in the 
product (in mg per unit dose or volume) should be a mandated part of the labelling of 
all CDMPs.  
 
                                            
2 Russo, E. B. and Marcu, J. (2017) ‘Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads’, Adv. 
Pharmacol., 80, pp 67–134. 
3 Ligresti. A., De Petrocellis, L. and Di Marzo, V. (2016) ‘From Phytocannabinoids to Cannabinoid Receptors and 
Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology’, Physiol. Rev., 96, pp 
1593–659. 
4 Izzo, A. A., Borrelli, F., Capasso, R., Di Marzo, V. and Mechoulam, R. (2009) ‘Non-psychotropic plant cannabinoids: new 
therapeutic opportunities from an ancient herb’, Trends Pharmacol. Sci., 30, pp 515–27. 
5 Allan, G. M., Ton, J. and Perry, D. (2018) ‘Evidence for THC versus CBD in cannabinoids. Pain, nausea and vomiting, 
spasticity, and harms’, Can. Fam. Physician, 64, p 519. 
 
6 Russo, E. and Guy, G. W. (2006) ‘A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol 
and cannabidiol’, Medical Hypotheses, 66, pp 234–246. 
7 Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R. and Fallon, M. T. (2010) ‘Multicenter, 
double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract 
and THC extract in patients with intractable cancer-related pain’, J. Pain Symptom Manage., 39 (2), pp 167–79.  
 
8 Bonomo, Y., Souza, J. D., Jackson, A, Crippa, J. A. S. and Solowij, N. (2018) ‘Clinical issues in cannabis use’, Br. J. Clin. 
Pharmacol.  
9 Lucas, C. J., Galettis, P. and Schneider, J. (2018) ‘The pharmacokinetics and the pharmacodynamics of cannabinoids’, Br. 
J. Clin. Pharmacol.  
10 Schleider, L. B., Abuhasira, R. and Novack, V. (2018) ‘Medical cannabis: aligning use to evidence-based medicine 
approach’, Br. J. Clin. Pharmacol.  
11 Abrams, D. I. (2018) ‘The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of 
Sciences, Engineering and Medicine report’, Eur. J. Intern. Med., 49, pp 7–11. 
12 Allan, G. M., Finley, C. R., Ton, J., Perry, D., Ramji, J., Crawford, K., Lindblad, A. J., Korownyk, C. and Kolber, M. R. 
(2018) ‘Systematic review of systematic reviews for medical cannabinoids: Pain, nausea and vomiting, spasticity, and harms’, 
Can. Fam. Physician, 64, pp e78–e94. 
13 Gaston, T. E. and Friedman, D. (2017) ‘Pharmacology of cannabinoids in the treatment of epilepsy’, Epilepsy Behav.,  70, 
pp 313–318.  

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Some CDMPs will contain, in addition to THC and CBD, a number of other compounds 
derived from Cannabis. At present, the evidence is unclear as to the therapeutic 
benefit or harms of these other compounds. As scientific understanding improves, the 
labelling of CDMPs with other compounds should be indicated.   
 
In the development of guidance, consideration should also be given to the following.   
• The acidic forms of some of the cannabinoids that exist in Cannabis. For 
example, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) 
can be converted to THC and CBD respectively by the act ion of heat. Specific 
methodology to ensure consistency of values on analysis could be stipulated. 
Alternatively, the total THC and total CBD amounts could be required to include 
both THC and CBD and their acids.   
• Ratios of the compounds present may be included on a label to help to reduce 
clinical errors.  
• An indication of variability  of the compounds  should be included , as CDMP 
materials will be derived from natural ingredients.  
 
Recommendation 5: The ACMD recommends that all CDMPs should have a clear 
content description. The description should, as a minimum requirement, state 
the content of CBD and THC  (in mg per unit dose or volume)  in a manner that 
would inform the prescriber when making a clinical decision . Consideration 
should be given to what additional information would be helpful to prescribers.  
 
Route of administration  
The ACMD previously identified potential risks related to inappropriate prescribing and 
diversion of CDMPs. In addition to providing a clear content description, the form and 
specific dosing instructions should, as with any other prescription, be clearly stated on 
the prescription. The ACMD recommends that the route of administration be included 
as an additional prescription requirement for CDMPs. The ACMD does not anticipate 
that smoking will be a permissible route of administration of a CDMP as there is 
evidence of harms associated with smoking Cannabis. 14 
 
Recommendation 6 The DHSC and NHS  England (and their equivalents in 
Scotland, Wales and Northern Ireland) to ensure that the route of administration 
is stated on prescriptions to help to ensure patient safety and reduce diversion. 
Producers of CDMPs should be required to state the appropriate route of 
consumption of their product. CDMPs should not be administered by smoking.   
  
Capturing clinical outcomes  
Expanding upon the Government’s intention to establish a national registry to capture 
levels of prescribing, the ACMD recommends that mechanisms should be set in place 
                                            
14 Lee, M. and Hancox, R. J. (2011) ‘Effects of smoking cannabis on lung function’, Expert Review of Respiratory Medicine, 
5:4, pp 537–547. 

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to collect, collate and publish the clinical outcomes of the prescription and use of 
CDMPs, as this will help to build understanding of their benefits and harms.  
 
Recommendation 7: The ACMD recommends that the DHSC (and its equivalents 
in Scotland, Wales an d Northern Ireland)  establishes mechanisms to capture 
and publish the clinical outcomes of the prescription and use of CDMPs.  
 
Clinical trials  
A programme of clinical trials should be co-ordinated:  
• to establish a credible evidence base to understand the  short- and long-term 
safety of using CDMPs;  
• to identify specific clinical conditions and indications; and  
• to enhance clinical decision making.  
 
Recommendation 8: The National Institute for Health Research (NIHR) to work 
with DHSC and NHS England (and their equivalents in Scotland, Wales and 
Northern Ireland) to co-ordinate and support a programme of clinical trials to 
establish a credible evidence base for short and long -term safety and clinical 
indications.  
 
Implementation and review of interim proposals 
 
Communications strategy 
At present the demand for CDMPs is unknown. However, judging from other countries 
that have made CDMPs available, the demand could potentially be high. The ACMD 
advises that the Government carefully consider s the likely demand in the UK. It is 
critical that there is clear information disseminated regarding the introduction of 
CDMPs prior to the implementation of the p roposed approach. The potential benefits 
and limitation s of prescribing CDMPs should be clearl y described for  clinicians, 
patients and their relatives prior to the introduction of CDMPs. Those responsible for 
law enforcement will also require information specific to these products. 
 
Recommendation 9: The Home Office, DHSC (and its equivalents in Scotland, 
Wales and Northern Ireland) and MHRA to develop a robust communications 
strategy for the public, clinicians and law enforcement to ensure that coherent 
messages are conveyed prior to and following the proposed rescheduling. This 
should clarify when these products are likely to be prescribed and the route by 
which they can be prescribed.   
 
Encouraging licensed products in an emerging CDMPs market  
The ACMD notes that the supply of unlicensed CDMPs will initially be largely through 
importation. It is  however likely that the UK market will develop . As the UK market 
matures, it is desirable that CDMPs with MHRA marketing authorisation  and 

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associated safety and quality checks become more widely available. To expedite the 
transition from the use of ‘specials’ to the use of licensed medicinal products, the 
Government should encourage pharmaceutical companies developing CDMPs to 
apply for MHRA marketing authorisation.  
 
Recommendation 10: The DHSC and MHRA to consider methods to enc ourage 
pharmaceutical companies to apply for MHRA marketing authorisation for 
CDMPs.  
 
Review of interim proposals 
The time interval between the proposed interim guidance and the development of the 
NICE guidance will provide an opportunity for the Government to explore international 
models on the clinical use of CDMPs. In addition to the ongoing ACMD work, the 
Government should review the outcomes and consequences of the proposed interim 
approach, including any changes in legislation. 
 
Recommendation 11: The Home Office and DHSC (and its equivalents in 
Scotland, Wales and Northern Ireland) to commit to undertaking an evidence -
based review of the proposed interim approach. The ACMD looks forward to the 
findings of this review being made available to inform our longer-term work.  
 
We would welcome the opportunity to discuss our conclusions and recommendations.  
 
Yours sincerely,  
 
 
Dr Owen Bowden-Jones 
Chair of the ACMD