Neil Smith [1] makes some interesting comments on our editorial [2] on cannabis potency in Europe that not only add usefully to the ongoing debate, but also illustrate further the complex set of issues with which this topic presents us. We would reiterate that, within this complexity, it is easy to forget the simple point we make in our original paper: it remains unclear that even if higher potency cannabis is available it may not necessarily lead to an increase dose exposure—and this remains an important issue for further research. Smith introduces the role of cannabidiol (CBD) as an interesting new dimension to the debate about cannabis potency. If we accept that CBD acts as an antagonist of Δ9-tetrahydrocannabinol (THC), then there would be some cause for concern if, as suggested, CBD levels have remained constant as the THC content of some forms of cannabis has increased. It is certainly true that while THC may be analysed routinely in many countries, few measurements are made of CBD. The only recent published data come from the University of Mississippi Project [3] where the levels of cannabinoids including THC and CBD were reported in cannabis, cannabis resin and other samples submitted for analysis over the period 1980–97. If we focus only on the cannabis samples (i.e. marihuana and sinsemilla) then there is a statistically significant positive correlation between the annual mean THC and CBD concentrations (r = 0.56; n = 36; P < 0.001). Only about 5% of the cannabis samples examined were sinsemilla. If these relatively few measurements are excluded, then the correlation coefficient for the annual means (THC: CBD, marihuana, n = 18) rises to r = 0.81. Within each correlation, we can assume that a large part of the statistical scatter arises from experimental uncertainties in the measurement of both THC and CBD. As discussed in our earlier report [4], there are a number of factors that currently lead to difficulties in the accurate analysis of THC. There will inevitably be additional uncertainties in the measurement of CBD. We conclude that this evidence shows that, at least in herbal cannabis, the level of CBD increases in parallel with THC rather than remaining constant. An aspect not mentioned by Smith is that CBD is present in much higher levels in cannabis resin. Based on the same data from ElSohly et al. [3], the average THC/CBD ratio in marihuana in that 18-year period was 12.2; in resin the ratio was closer to unity. In other words, if CBD offers some protective effect against THC then we should expect that those who smoke resin would suffer less harm than those who smoke herbal cannabis. As far as we are aware, no studies have been carried out that could shed light on this hypothesis. A caveat must be included that the situation regarding THC/CBD ratios found in the United States may differ from those in Europe if only because both cannabis and cannabis resin in the United States originate from different geographical areas to those products in Europe. The suggestion by Smith that the half-life of cannabinoids might be affected by potency seems less convincing. It is misleading to say that ‘lower potency cannabis has been shown to have a half-life of around 20–30 hours in human participants…’. It is only meaningful to refer to the half-lives of specified psychoactive substances. The plasma half-life of THC is 1.5–2 hours [5]. By contrast, THC metabolites may be detected in the urine for up to 1 or 2 weeks. By analogy with other drugs, we might expect that a higher body burden of a foreign substance could saturate the metabolic systems responsible for degradation and would therefore lead to a longer, not a shorter half-life. The analogy of the benzodiazepines is equally misleading because they represent a family of chemically and pharmacologically distinct entities. There is no evidence that the active constituents in high-potency cannabis are qualitatively different to those in low potency material. Finally, we stand by our comment that the facts of this matter, as weak as they may be, are less alarming than they have sometimes been presented. This does not mean that we are suggesting we should be complacent on this issue. We recognize that important questions for public health are raised by current cannabis consumption patterns, and our editorial identifies a number of important information needs. However, if complacency may not be called for, scientific caution certainly is; a meaningful public health debate on cannabis use is not possible if the evidence it is based on is found, when scrutinized, to be lacking.
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