This originally appeared at https://pubmed.ncbi.nlm.nih.gov/24175484/

Abstract

Cannabinoids, including tetrahydrocannabinol and cannabidiol, are the most important active constituents of the cannabis plant. Over recent years, cannabinoid-based medicines (CBMs) have become increasingly available to patients in many countries, both as pharmaceutical products and as herbal cannabis (marijuana). While there seems to be a demand for multiple cannabinoid-based therapeutic products, specifically for symptomatic amelioration in chronic diseases, therapeutic effects of different CBMs have only been directly compared in a few clinical studies. The survey presented here was performed by the International Association for Cannabinoid Medicines (IACM), and is meant to contribute to the understanding of cannabinoid-based medicine by asking patients who used cannabis or cannabinoids detailed questions about their experiences with different methods of intake. The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoidbased medicine performed so far. In general, herbal non-pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids. However, the number of patients who reported experience with pharmaceutical products was low, limiting conclusions on preferences. Nevertheless, the reported data may be useful for further development of safe and effective medications based on cannabis and single cannabinoids.

Conclusion:

To our knowledge, this survey represents the largest systematic study of patient experiences with CBMs con-
ducted to date. Although other, and sometimes larger, surveys have been reported, they did not compare patients’
experiences with multiple CBM products or administrations forms, or they were restricted to a single country
and/or focused on a single medical condition (Hazekamp 2013; Corless 2009; O’Connell 2007; Chong 2006; Ware
2005; Prentiss 2004; Page 2003; Ware 2003; Braitstein 2001; Ogborne 2000). The majority of subjects in our
study were current users who had a health professional involved in the management of their illness, and were using
CBMs for at least several years. The inclusion criterion that participants should have experience with at least two
administration forms was easily met in the study population; on average, those who (ever) tried smoking cannabis
had experience with 2.4 different administration forms (lowest value), while those who had (ever) used nabiximols
(Sativex® ) had tried 4.4 different administration forms (highest value) in total.

The main goal of this survey was to compare different administration forms of cannabinoids and identify their rel-
ative advantages and disadvantages as described by actual users. Before any conclusions may be drawn, however, the
potential limitations of the study must be clearly addressed. Most participants of the survey had experience with herbal
cannabis before onset of their medical condition, and smoking of cannabis was the most common method of intake
participants had tried. So although many different methods of intake were represented in the survey, the results may
be biased towards the use of herbal cannabis. Also, people who were satisfied with their first cannabinoid medication
(e.g., smoked cannabis, dronabinol, nabiximols) and used it without problems were not included, because they did
not meet the inclusion criterion of having experience with multiple methods of intake. As homemade cannabis prod-
ucts allow more experimentation with administration forms and dosing than standardized oral products, the survey con-
sequently may have favored participants who use herbal cannabis. Because of this potential for bias, we caution
against drawing any conclusions with respect to the efficacy of any CBM from this study. In addition, circulating
the survey through the IACM may have attracted responses from subjects who are already familiar with cannabis
effects and may have produced a bias towards more positive responses overall. In addition, one should keep in mind
that some CBMs (such as nabiximols) have been available to patients only for a relatively short time. But despite these
limitations, we believe that these results contribute to our understanding of patient preferences for specific methods
of intake (administration forms) for cannabinoids.

Patient-reported advantages and disadvantages for each administration form varied widely. Many parameters measured (e.g., time before first onset, duration of effects) showed a distinction between oral and inhaled forms of cannabinoids, reflecting known differences in pharmacokinetics and/or pharmacodynamics. Nabiximols was often rated between oral and inhaled administration, reflecting the different nature of the oromucosal administration form. Many participants also provided scores in the category “other use,” suggesting there may have been administration forms that were overlooked in this study. Future surveys may want to further identify such products.

In general, products in Group 1 (i.e., herbal non-pharmaceutical CBMs) received the higher scores in most categories. Products of Group 2 (i.e., pharmaceutical, standardized products) scored consistently higher than the herbal preparations only for “ease of preparation and intake.” Indeed, herbal products are generally lacking convenient, reliable, and standardized administration forms, in contrast to conventional approved medicines.

There was low patient satisfaction with costs for all CBMs studied. This may be because most healthcare systems do not provide for reimbursement or health insurance coverage of CBMs, with the exception of the

Dutch program, where cannabis is covered by an increasing number of health insurers (NCSM 2012), and Canada
where nabilone is covered on most provincial formularies. Indeed, cost factors may have influenced our data:
when medication costs are covered by health insurance, patients may be able to use higher doses. Conversely, when
patients have to cover the costs by themselves (probably most often when cannabis is used without prescription)
the doses used may be lower. Perhaps those patients preferring herbal cannabis are those who need a very high
dose of cannabinoids, which cannot be covered by the currently available pharmaceutical cannabinoid preparations,
both practically and economically. As a result, costs may also be a reason for patients to grow their own cannabis.

The source where CBMs are obtained is worth further consideration, as we found that homegrowing is very
popular despite clear legal risks in most countries. Patients who use CBMs on prescription, and simultaneously grow
their own cannabis, may raise questions about the legitimacy of their medical use of cannabinoids. For researchers
as well as policy makers, it would be of interest to under-stand the motivations for patients to choose a particular
source of herbal CBMs. Besides cost, another potential rea-son for continuing home-growing despite having access to
a legal source may be a lack of cannabis varieties currently available to patients. Indeed, differences in chemical com-
position between varieties can be significant (Fischedick 2010; Hazekamp 2012). In Canada, a recent review of the
national medical marijuana program indicated that access to multiple cannabis varieties is an important issue for
patients (Health Canada 2011).

In conclusion, we believe that this survey presents a broad picture of the current state of CBM use. The reported
data may be useful to guide the development of safe and effective cannabinoidbased medications that meet the
needs of patients. Besides the need for such products to be standardized and quality controlled, our data suggest that
overall there is good satisfaction with whole plant preparations that are affordable and administered in an inhaled
manner, or in the form of a tincture. Relatively new administration forms of herbal cannabis, such as juicing of raw
leaves and buds (Courtney 2012), or the preparation of concentrated extracts such as Simpson oil (Simpson 2012), are
not covered by this survey. Future studies should therefore be aware of these newer cannabis preparations, and ask
more detailed questions in order to properly explore such upcoming cannabinoid based treatments.