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Potency and Therapeutic THC and CBD Ratios: U.S. Cannabis Markets Overshoot

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Frontiers in Pharmacology
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Background and aims: The effects exuded by cannabis are a result of the cannabinoids trans-Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), and is dependent upon their pharmacological interaction and linked to the two cannabinoids’ concentrations and ratios. Based on current literature and trends of increasing cannabis potency, we postulate that most medical cannabis products with THC and CBD have ratios capable of producing significant acute intoxication and are similar to recreational products. We will test this by organizing products into clinically distinct categories according to TCH:CBD ratios, evaluating the data in terms of therapeutic potential, and comparing the data obtained from medical and recreational programs and from states with differing market policies. Methods: We utilized data encompassing online herbal dispensary product offerings from nine U.S. states. The products were analyzed after being divided into four clinically significant THC:CBD ratio categories identified based on the literature: CBD can enhance THC effects (THC:CBD ratios ≥1:1), CBD has no significant effect on THC effects (ratios ∼ 1:2), CBD can either have no effect or can mitigate THC effects (ratios 1:>2 < 6), or CBD is protective against THC effects (ratios ≤1:6). Results: A significant number of products (58.5%) did not contain any information on CBD content. Across all states sampled, the majority (72–100%) of both medical and recreational products with CBD (>0%) fall into the most intoxicating ratio category (≥1:1 THC:CBD), with CBD likely enhancing THC’s acute effects. The least intoxicating categories (1:>2 < 6 and ≤1:6 THC:CBD) provided the smallest number of products. Similarly, the majority of products without CBD (0%) contained highly potent amounts of THC (>15%). These results were consistent, regardless of differing market policies in place. Conclusions: Despite the distinct goals of medical and recreational cannabis users, medical and recreational program product offerings are nearly identical. Patients seeking therapeutic benefits from herbal cannabis products are therefore at a substantial risk of unwanted side effects, regardless of whether they obtain products from medical or recreational programs. Efforts are needed to better inform patients of the risks associated with high potency cannabis and the interaction between THC and CBD, and to help shape policies that promote more therapeutic options.
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Potency and Therapeutic THC and
CBD Ratios: U.S. Cannabis Markets
Overshoot
Sarah D. Pennypacker
1
, Katharine Cunnane
1
, Mary Catherine Cash
1
,
2
and
E. Alfonso Romero-Sandoval
1
*
1
Department of Anesthesiology, Pain Mechanisms Laboratory, Wake Forest University School of Medicine, Winston-Salem, NC,
United States,
2
Department of Pharmacy, Wake Forest University School of Medicine, Winston-Salem, NC, United States
Background and aims: The effects exuded by cannabis are a result of the cannabinoids trans-
Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), and is dependent upon their
pharmacological interaction and linked to the two cannabinoidsconcentrations and ratios.
Based on current literature and trends of increasing cannabis potency, we postulate that most
medical cannabis products with THC and CBD have ratios capable of producing signicant
acute intoxication and are similar to recreational products. We will test this by organizing
products into clinically distinct categories according to TCH:CBD ratios, evaluating the data in
terms of therapeutic potential, and comparing the data obtained from medical and recreational
programs and from states with differing market policies.
Methods: We utilized data encompassing online herbal dispensary product offerings from nine
U.S. states. The products were analyzed after being divided into four clinically signicant THC:
CBD ratio categories identied based on the literature: CBD can enhance THC effects (THC:
CBD ratios 1:1), CBD has no signicant effect on THC effects (ratios ~ 1:2), CBD can either
have no effect or can mitigate THC effects (ratios 1:>2<6), or CBD is protective against THC
effects (ratios 1:6).
Results: Asignicant number of products (58.5%) did not contain any information on CBD
content. Across all states sampled, the majority (72100%) of both medical and recreational
products with CBD (>0%) fall into the most intoxicating ratio category (1:1 THC:CBD), with
CBD likely enhancing THCs acute effects. The least intoxicating categories (1:>2<6and1:6
THC:CBD) provided the smallest number of products. Similarly, the majority of products without
CBD (0%) contained highly potent amounts of THC (>15%). These results were consistent,
regardless of differing market policies in place.
Conclusions: Despite the distinct goals of medical and recreational cannabis users, medical
and recreational program product offerings are nearly identical. Patients seeking therapeutic
benets from herbal cannabis products are therefore at a substantial risk of unwanted side
effects, regardless of whether they obtain products from medical or recreational programs.
Efforts are needed to better inform patients of the risks associated with high potency cannabis
and the interaction between THC and CBD, and to help shape policies that promote more
therapeutic options.
Edited by:
Francesca Baratta,
University of Turin, Italy
Reviewed by:
Vanessa Minervini,
Creighton University, United States
Paolo Tucci,
University of Foggia, Italy
*Correspondence:
E. Alfonso Romero-Sandoval
earomero.sandoval@gmail.com
Specialty section:
This article was submitted to
Ethnopharmacology,
a section of the journal
Frontiers in Pharmacology
Received: 15 April 2022
Accepted: 20 May 2022
Published: 06 June 2022
Citation:
Pennypacker SD, Cunnane K,
Cash MC and Romero-Sandoval EA
(2022) Potency and Therapeutic THC
and CBD Ratios: U.S. Cannabis
Markets Overshoot.
Front. Pharmacol. 13:921493.
doi: 10.3389/fphar.2022.921493
Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214931
ORIGINAL RESEARCH
published: 06 June 2022
doi: 10.3389/fphar.2022.921493
Keywords: cannabidiol, tetrahydrocannabinol, marijuana, medical marijuana, herbal cannabis, cannabis market,
potency, intoxication
INTRODUCTION
Trans-Δ
9
-tetrahydrocannabinol (THC) and cannabidiol (CBD)
are the two most prominent cannabinoids that comprise cannabis
(Elsohly et al., 2014). The pharmacologic effects they each exude
are quite distinct. For instance, CBD does not produce acute
intoxication, has been proven to treat refractory epileptic
syndromes in children, and may have anti-inammatory,
anxiolytic, and antipsychotic indications (Zuardi et al., 1993;
Bergamaschi et al., 2011a;Bergamaschi et al., 2011b;Leweke
et al., 2012;Iseger and Bossong, 2015;Devinsky et al., 2017). Yet,
there is currently no substantial evidence that CBD alone has
analgesic efcacy in humansthe primary indication for which
patients seek out cannabis in the United States (U.S.) (Boehnke
et al., 2019). On the other hand, THC produces the acute
intoxication associated with cannabis and has been linked to
multiple undesirable effects, such as paranoia, memory
impairment, increased risk for psychotic illness, and cannabis
dependency and the development of cannabis use disorder
(CUD) (Di Forti et al., 2009;Izzo et al., 2009;Freeman et al.,
2014).
Notably though, THC has shown promising analgesic efcacy
(Abrams et al., 2007;Ellis et al., 2009;Ware et al., 2010;Wilsey
et al., 2013;Wallace et al., 2015;Wilsey et al., 2016;van de Donk
et al., 2019). This analgesic effect of THC is still under
investigation (Boehnke and Clauw, 2019) but likely mirrors
THCs concentration and thus cannabisintoxication potential
(Wilsey et al., 2013;Andreae et al., 2015;Wallace et al., 2015;van
de Donk et al., 2019). In clinical trials studying the analgesic
efcacy for cannabis, the THC concentrations utilized are
consistently <10% (Abrams et al., 2007;Ellis et al., 2009;Ware
et al., 2010;Wilsey et al., 2013;Wallace et al., 2015;Wilsey et al.,
2016). In fact, signicantly lower THC concentrations (13%)
were used in several of the studies and resulted in sufcient
clinical efcacy to manage pain (Wilsey et al., 2013;Wallace et al.,
2015;Wilsey et al., 2016). Furthermore, adverse event potential
and subsequent treatment discontinuation seems to increase at
higher THC concentrations utilized in these studies. This parallel
between THC concentration and intoxication and adverse event
potential is increasingly becoming an issue as the potency of
cannabis available rises (ElSohly et al., 2016;Chandra et al., 2019)
despite patients often wishing to experience therapeutic benets
of THC without the associated subjective side effects (Joy et al.,
1999;Grotenhermen, 2004;Hall, 2015). As a result, a difcult
balancing act between analgesia and acute intoxication ensues.
Still, cannabis with high concentrations of THC (>15%) and
greater intoxication potential is often favored in the recreational
realm (Romero-Sandoval et al., 2018) and is associated with
worse chronic pain in regular users (Boehnke et al., 2020).
This discrepancy between the goals of medical and
recreational products presumably should be reected in the
potency of the products each type of market offers. However,
our previous ndings demonstrated that average THC
concentrations advertised online in medical programs are
similar to those in recreational programs (Cash et al., 2020).
Moreover, frequent medical cannabis users prefer inhaled
cannabis with high levels of THC (Boehnke et al., 2020). The
accessibility of high potency products could create a
misconception about the safety of cannabis and downplay the
risks and side effects associated with products containing high
THC concentrations. It also leaves patients looking to use
cannabis for medical purposes with mostly products outside
the realm of what is considered potentially suitable for
therapeutic purposes (Romero-Sandoval et al., 2018). It is
important to note that while there may be some patients who
enjoy the highor are willing to assume the risk of high THC
consumption (as it may happen with opioids), this is not
recommended from a medical standpoint. This sentiment is
strongly supported by the International Association for the
Study of Pain (IASP), which recently released a report which
concluded that much more research is needed to determine the
benets and risks of cannabis for the treatment of pain before
there is a chance cannabis can be endorsed for such usage (IASP
Presidential Task Force on Cannabis and Cannabinoid Analgesia,
2021).
While these previous ndings are certainly alarming, they only
show a partial picture of the cannabis products offered in legal
U.S. markets. CBD has long been proven to alter cannabiseffects,
and while CBD data was presented alongside THC
concentrations categories in our previous study, the data was
not thoroughly analyzed in relation to THC:CBD ratios and
concentrations (Cash et al., 2020). Literature suggests that
different concentrations of THC and CBD and different ratios
of THC:CBD induce variances in experienced subjective effects
(Pennypacker and Romero-Sandoval, 2020). In fact, it appears
that certain lower ratios of THC:CBD are more apt to produce an
attenuation of THC induced effects (Dalton et al., 1976;Englund
et al., 2013;van de Donk et al., 2019) while higher ratios are more
likely to enhance THC induced effects (Arkell et al., 2019;Solowij
et al., 2019;van de Donk et al., 2019). For instance, one study
found that inhaled cannabis at a 2:1 THC:CBD ratio (8 mg THC
(1.6%)/4 mg CBD (0.8%)) enhanced the subjectsintoxication
when compared with THC alone (8 mg), but a 1:20 THC:CBD
ratio (8 mg THC (1.6%)/400 mg CBD (80%)) reduced the
subjectsintoxication when compared with THC alone (8 mg)
(van de Donk et al., 2019). Notably, these ndings are
counterintuitive to the popular idea that CBD is simply
protective against the intoxicating effects of THC, that CBD is
the yin to THCs yang.
It is therefore important to determine whether the products
available in dispensaries are pharmacologically safe for patients
(medicinal) or the general public (adult use or recreational), not
only by means of THC concentrations, but also CBD
concentrations and the ratio of THC:CBD. Our previous
ndings clearly show that when analyzing the types of
products offered in legal cannabis markets based solely on
Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214932
Pennypacker et al. Potency and THC:CBD Ratios
THC, the majority of products contain levels not recommended
(i.e., >15% THC) since they are associated with strong
intoxicating effects (Cash et al., 2020). However, we wonder
whether the combination of these high THC levels with
certain CBD concentrations and/or the ratio of THC:CBD
could result in a pharmacological interaction that reduces the
risk of high levels of THC. We identied some products that are
more pharmacologically amenable to medical purposes, based on
their THC levels (i.e., <10%) (Cash et al., 2020); but it is also
possible that these products will contain THC:CBD ratios that
lead to a pharmacologic interaction that enhances THC
intoxicating effects (Pennypacker and Romero-Sandoval,
2020). In other words, it is clinically relevant to garner
whether or not the existing products contain these two
cannabinoids at concentrations and ratios that are suitable for
patients. Specically, it is necessary to determine if CBD at the
levels available in dispensaries will exude pharmacologic
protective/benecial effects or detrimental effects to established
THC liabilities (e.g., stronger intoxication, withdrawal, tolerance,
dependence, addiction, psychiatric issues, etc.).
Since medical cannabis programs mimic recreational programs,
we hypothesize that ratios and concentrations of CBD in products
available in medical cannabis programs are similar to that in
recreational cannabis programs, with the majority at levels which
will likely enhance THCs subjective effects. This study subsequently
will test this hypothesis following these aims: 1) identify and
categorize the THC:CBD ratios associated with different clinically
meaningful pharmacologic effects when administered in
conjunction via inhalation, 2) characterize the cannabis products
available online within the determined ratio categories, 3) evaluate
whether the probable pharmacologic effects of products labeled as
recreational differ from the probable effects of products labeled as
medical, and 4) determine if varying types of market structures (e.g.,
medical and recreational products offered in same facility or in
separate facilities) provide clinically different cannabis offerings
based on THC:CBD ratios.
MATERIALS AND METHODS
Data Collection
We utilized the publicly available data set from our previously
published study (Cash et al., 2020). To summarize, states with
legalized medical and/or recreational programs that have legalized
cannabis for pain management were identied. The data sampling
included online dispensary product offerings from nine U.S. states
and spanned two distinct geographical locations: the Northeast
region [Maine (ME), Massachusetts (MA), New Hampshire
(NH), Rhode Island (RI) and Vermont (VT)] and the Western
region [California (CA), Colorado (CO), New Mexico (NM),
Washington (WA)] of the United States (U.S.). At the time of
sampling, all of the Northeastern states as well as NM had legalized
only the medical use of cannabis, and CA, CO, and WA had legalized
cannabis for both medical and recreational use. Additionally,
medical and recreational products were offered in separate
facilities in WA, while both medical and recreational products
were allowed to be offered in the same building in CO, and
products were not differentiated medical or recreational in CA.
Inhaled cannabis has a more favorable pharmacokinetic prole than
otherroutesofadministrationandhasshownanalgesicefcacy for
various chronic pain conditions, the most common reason cited for
seeking out medical marijuana in the U.S. (Wilsey et al., 2013;
Andreae et al., 2015;Wallace et al., 2015;Romero-Sandoval et al.,
2018). Herbal products (owers and pre-rolls) were therefore the
focus of the sampling. Individual product cannabinoid data (THC
and CBD content) was recorded.
Ratio Categorization
In order to carry out the rst study aim, and based on our previous
observations (Pennypacker and Romero-Sandoval, 2020), we
identied four clinically signicant THC:CBD ratio categories:
CBD can enhance THC effects (THC:CBD ratios 1:1), CBD has
no signicant effect on THC effects (ratios ~1:2), CBD can either
have no effect or is protective against THC effects (ratios 1:>2<6), or
CBD is protective against THC effects (ratios 1:6). Products with
THC:CBD ratios >0.7 were considered to fall into the rst category,
1:1. Products with THC:CBD ratios 0.4 and <0.7 were considered
to fall into the second category, ~ 1:2. Products with THC:CBD
ratios <0.4 and >0.167 were considered to fall into the third category,
1:>2<6. And nally, products with THC:CBD ratios 0.167 were
considered to fall into the fourth category, 1:6. While further
investigation into concomitant administration of THC and CBD,
their pharmacological interaction, and the resulting effects is
certainly needed, this theme remained consistent throughout a
thorough review of the literature (Pennypacker and Romero-
Sandoval, 2020).
Statistical Analysis
Mean and standard deviation analysis was performed for each state
and for distinct medical and recreational program comparisons. The
four clinically signicant THC:CBD ratio categories, 1:1, ~1:2, 1:>2
<6, and 1:6, were analyzed for each state and program type. Either
Students T test or One-way ANOVA and Turkeysmultiple
comparison test were used, and a p<0.05 was considered
statistically signicant. Relevant data is presented as (mean ± SD;
median 25% percentile, 75% percentile).
RESULTS
Our results come from 8,534 herbal cannabis products (we did not
exclude any product based on THC concentration) and their THC
and CBD concentration information (Cash et al., 2020). These
products were obtained from 653 dispensarieswebsites from
nine states; CA (n= 606 total products), CO (n=545for
medical, n= 707 for recreational), ME (n=37),MA(n=332),
NH (n= 106), NM (n=668),RI(n=49),VT(n=21),WA(n=
2,834 for medical, n= 2,629 for recreational). We found that most of
these products, 58.5%, do not have any CBD content information. Of
the 3,545 products with CBD content information (41.5% of all
surveyed products), 839 (26.5% of products with CBD information)
reported 0% content and 2,606 (73.5% of products with CBD
information) reported >0% CBD concentration . The proportion
of products with no CBD content, with 0% CBD content, and with
Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214933
Pennypacker et al. Potency and THC:CBD Ratios
>0% CBD content information varies widely among states
(Figure 1).
For subsequent analysis, we used only products with >0% CBD
content, unless otherwise indicated. We noticed that not all
evaluated states offered products belonging to all four THC:CBD
categories we consider clinically meaningful. However, all the states
offer products from the THC:CBD ratios 1:1 category (CBD
enhances THC effects, Figure 2). In fact, and in line with our
hypothesis, the majority of both medical and recreational products
analyzed (72100%) fall into the foremost listed category, with CBD
likely potentiating THC effects; and products likely to provide CBD
mitigation of THC effects (THC:CBD ratios 1:6) make up the
smallest category (05%, Figure 2).
Intriguingly, the majority of products within the THC:CBD ratios
1:1 category have >15% THC, a concentration that is highly
intoxicating, in all states, with the exception of VT where
products contain <10% THC (Figure 3). All other THC:CBD
ratio categories are comprised of products with <10% THC in all
studied states (Figure 3).
We observed that products with CBD information containing 0%
CBD (839 products), have in average >15% THC in all states with
these products (NH, RI, and VT did not have this type of product);
with NM, CA, CO (Medical and Recreational), and WA (Medical
and Recreational) containing >20% and ME and MA containing
16.5 and 19.3% THC in average respectively (Figure 4). When
products with CBD information containing <15% THC were
examined (417 products deemed more suitable for medical
purposes), we observed that the majority of products fall into the
~1:2,1:>2<6, and 1:6 ratio categories in all states except in ME
where 1:1 products dominate; the THC average ranges from 69%
and CBD averages from 611%, except in ME where THC and CBD
averages were 11.7 and 1.4% respectively (Figure 4). Potent products
FIGURE 1 | Proportion of products by CBD content information provided per state. Total products sampled per state listed below each graph.
FIGURE 2 | Proportion of products within THC:CBD ratio categories per state. Total products per state listed below each graph.
Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214934
Pennypacker et al. Potency and THC:CBD Ratios
with >15% THC and CBD information were very similar to products
with 0% CBD, namely containing in average >20% THC in all cases,
except in ME (18% THC average), and VT (did not have products in
this category), and <1% CBD levels in all states, except in CO
Medical (1.5% CBD average; Figure 4).
DISCUSSION
Overall, this studys results are alarming. They reveal current product
offerings do not reect scientic evidence regarding what
concentrations of THC and CBD could be potentially
therapeutic. Combined with holes in popular knowledge and
misconceptions about THC and CBD, the current market can
lead to problematic patient dosing as they try to maximize
therapeutic benets, such as analgesia, while subjecting
themselves to THCs acute intoxicating effects. For instance,
across all states, the vast majority of both medical and
recreational products with CBD (>0%) fall into the THC:CBD
ratio category 1:1, with CBD likely enhancing THC subjective
effects. The THC:CBD categories 1:6 and 1:>2<6, those with the
lowest intoxication potential, provide the least amount of products. It
is notable that products with lower THC, considered suitable for
medical purposes, might in fact not have signicant analgesic value
(Dalton et al., 1976;van de Donk et al., 2019),sincetheyhaveTHC:
CBD ratios of 1:6 or 1:>2<6, where CBD would likely reduce THC
effects. More potent products that may be suitable for regular users
or patients who have developed tolerance, those with 1015% THC
and ratios 1:1 and ~ 1:2, are difcult to nd in two major medical
programs (CO and WA) when compared to >15% THC products.
This leaves patients with mostly highly intoxicating options.
Moreover, these ndings are consistent across both medicinal
and recreational programs, andinmarketsthatofferboth
medical and recreational products (e.g., CA), or where all
products are considered medical (e.g., NM). These ndings also
remain true regardless of whether they coexist in the same building
(e.g., CO), or if they are in separated facilities (e.g., WA).
As shown, despite CBD having long been proven to
pharmacologically alter cannabisoverall effects, a large portion of
products did not provide information on CBD content. This could
potentially lead to unwanted side effects as patients do not have all
the information on the drug they are taking. The results reveal that
FIGURE 3 | THC and CBD percent distribution by ratio category for all products with >0% CBD in each state. Data shown as mean ± SD.
Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214935
Pennypacker et al. Potency and THC:CBD Ratios
products with 0% CBD are very potent (Figure 4), with most
products containing >15% THC, and virtually all containing close
to or >10% THC. These products, especially those with >15% THC
are counter indicated clinically and are therefore not recommended
or safe to be marketed as medical cannabis (Romero-Sandoval et al.,
2018;Boehnke et al., 2020;Cash et al., 2020). Similarly, products with
CBD and >15% THC overwhelmingly behave similarly to those
without any CBD. Virtually all of these high potency products
contain <1% CBD, with mean values close to 0%. Consequently,
products with high THC are likely to have little CBD. This theme can
be helpful to note, especially for the signicant number of products
that do not offer information on CBD content. There are a few
product exceptions in Washington medical and Colorado medical
programs where there is more variation in CBD content, even in the
high potency products. While there are certainly not enough of these
outlying products to change the overall market makeup, this
variation seems to indicate that medical programs recognize a
demand for products different than those in the recreational
market. Still, based on the literature, these products with high
potency THC and high CBD concentrations likely produce
signicant unwanted psychotropic effects and can be harmful to
patients seeking chronic pain relief (Wilsey et al., 2013;Andreae
et al., 2015;Wallace et al., 2015;Boehnke et al., 2020;Pennypacker
and Romero-Sandoval, 2020).
Beyond recent research demonstrating the effects of cannabis
constituents, the momentum of current policy trends elicits a
pressing need to understand the clinical therapeutic value of the
cannabis available in the emerging market. As of February 2022, 37
states have legalized the medical usage of cannabis, and 18 states and
Washington, D.C. have fully legalized cannabis (for both medical
and recreational usage). Meanwhile, the rise of the opioid epidemic
in U.S. has placed pain management under scrutiny and jumpstarted
the search for treatment options with less adverse effects. Cannabis is
advantageously place to be, and is often cited as an one of these
alternatives (Caldera, 2020). In fact, presence of medical cannabis
programs may be associated with a reduced opioid usage (Lucas,
2017). In the midst of the U.S. cannabis marketsrapid evolution and
the changing attitudes towards traditional pain management, fully
understanding what cannabis products are offered from a
pharmacologic perspective could both better inform patients and
providers, and potentially shape usage and the future of the U.S.
cannabis market.
We understand that our data show advertised products rather
than consumer acquired products. However, our data matches the
natural supply and demand dynamic of any commodity, for which
cannabis is not an exception. Thus, the frequency of products
identied in our study in terms of THC and CBD concentrations
encompasses the frequency of product sales describe by others
(Smartetal.,2017;Davenport, 2021). Furthermore, our data
(frequency of potent herbal products) align with data on
cannabis exposure from the National Poison Data System which
shows that exposures more often involves plant material than other
processed forms of cannabis products (e.g., edibles, concentrates,
etc.) and this happens more often in states where adult cannabis use
FIGURE 4 | All individual products with CBD content information with corresponding THC and CBD percentage in each state. The rst column for each graph
contains all products with 0% CBD and their corresponding THC content; the second and third columns contain products with >0% CBD, with the second column
containing products with 15% THC, and the third column containing products with >15% THC.
Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214936
Pennypacker et al. Potency and THC:CBD Ratios
(recreational) is legal (Dilley et al., 2021). Similarly, it is important to
note that the data used in this study was collected in 2018 (Cash et al.,
2020). This is a limitation of the study as some of the data may have
changed. However, the trends on market behavior this paper
highlights are still relevant. If there are any pertinent changes,
they are likely detrimental as the potency of cannabis has
continually been increasing over the past several decades (ElSohly
et al., 2016;Chandra et al., 2019;ElSohly et al., 2021). These themes
are not limited to just the herbal market, but have been reected in
theediblecannabismarketaswell(Steigerwald et al., 2018). It is also
relevant to highlight the expansion of the CBD product market. We
do not know the extent to which CBD shops are inuencing the
presence of CBD in herbal cannabis products that have THC.
According to trends found in illicit herbal cannabis products
seized by the Drug Enforcement Administration, THCs average
potency ( ~ 4% in 1995, 9.75% in 2009, and 13.88% in 2019)
continues to rise and outpace CBD content ( ~ 0.28% in 2001, 0.39%
in 2009, and 0.56% 2019) (ElSohly et al., 2016;ElSohly et al., 2021).
There was a substantial increase in the average THC:CBD ratio from
2009 to 2017 (24.81103.48 respectively) which reversed in 2018
(54.39) and 2019 (24.58) (ElSohly et al., 2021). This reversal is
potentially a result of the expanding legalization of marijuana and
CBD product market, both of which should be reected in this
studys data based on the timeframe. We therefore believe that this
data is still highly relevant and reective of the current market
overall.
Furthermore, it is important to recognize that while this studys
results are concerning, they can also be seen as promising. In
addition to the decreasing ratio recently noted, clinically
meaningful optionsthose that can likely prove benecial to
patientsare offered in all states; they are just in the minority
and need to be teased out. The hurdles ahead to salvage the medical
cannabis market seem to be in two categories. First, changing public
misconceptions about THC and CBDs interplay and perceptions of
what THC and CBD percentages clinically correlate too. Specically,
there is a need for education emphasizing that different
concentrations of THC and CBD correlate to different
pharmacologic effects, that adding high concentrations of CBD
does not negate the psychotropic effects of THC, and that high
potency cannabis (>15% THC) is in fact counter indicated for
medical use. This will result in a more informed patient
population. It can also help sway the demand away from high
potency products and reduce incentives for the cannabis market to
continually increase the potency of their offerings. Secondly,
adequate policies regarding medical cannabis should also reect
the pharmacology and clinical correlates. This can be achieved
through several means. By enforcing that products advertised for
medical purposes actually have efcacy based on scienticliterature,
new policies can help expose the medically relevant products and
segregate them from the recreational products. This could prove
extremely meaningful, as it has been shown that patients regard the
information provided by dispensaries as safe and reliable (Capler
et al., 2017). Policies can also highlight the various clinically relevant
ratios, eshing out and offering substantial options in the
therapeutically relevant categories. Lastly, policies can recommend
dispensing medical products in a stepwise fashion, with the more
potent products offered on a more stringent basis, such as after lower
potency options proved ineffective for a patient. This can ensure an
overall safer market for patients looking to achieve therapeutic
benets from cannabis without the risk of amplifying THC acute
effects.
CONCLUSION
In summary, medical cannabis programsmirror recreational
cannabis programsherbal product offerings in terms of
pharmacological prole, and do so regardless of facility type.
An evaluation of these productsratios and concentrations
revealed that the majority are highly potent (>15% THC) and
contain THC:CBD ratios that will likely produce an additive
effect on THCs effects (1:1). And while analgesic effects likely
parallel THCs potency, so does intoxication and the frequency of
adverse events (Wilsey et al., 2013;Andreae et al., 2015;Wallace
et al., 2015;van de Donk et al., 2019). Therefore, many of the
products marketed for medical purposes are counter indicated
pharmacologically and potentially harmful (Romero-Sandoval
et al., 2018;Boehnke et al., 2020). On the other hand, options
that are likely the most suitable for therapeutic use are limited,
even in medical programs. Ultimately, these results can be used to
better inform patient populations and relevant policies and help
steer the herbal medical cannabis market to be more reective of
clinical evidence.
DATA AVAILABILITY STATEMENT
Publicly available datasets were analyzed in this study. This data can
be found here: https://doi.org/10.1371/journal.pone.0230167.s018.
AUTHOR CONTRIBUTIONS
Conceptualization: SP and ER-S. Data curation: KC, MC, and ER-S.
Formal analysis: SP and ER-S. Funding acquisition: ER-S.
Investigation: SP and ER-S. Methodology: ER-S. Project
administration: ER-S. Resources: ER-S. Supervision: ER-S.
Writingoriginal draft: SP and ER-S. Writingreview and
editing: SP and ER-S.
FUNDING
Department of Anesthesiology and Pilot Research Award by the
Center for Addiction Research, Wake Forest University School of
Medicine.
ACKNOWLEDGMENTS
Department of Anesthesiology, Department of Biostatistics and
Data Science, Department of Social Sciences and Health Policy,
and Center for Addiction Research at Wake Forest University
School of Medicine.
Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214937
Pennypacker et al. Potency and THC:CBD Ratios
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Conict of Interest: The authors declare that the research was conducted in the
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potential conict of interest.
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Frontiers in Pharmacology | www.frontiersin.org June 2022 | Volume 13 | Article 9214939
Pennypacker et al. Potency and THC:CBD Ratios
... Low THC: Cultivated for non-psychoactive properties (Pennypacker et al., 2022) (Fig. 1). ...
... Balanced strains: Some cannabis varieties contain about equal quantities of the cannabinoids THC and CBD (Pennypacker et al., 2022). ...
Chapter
Medicinal and aromatic plants (MAPs) have been treasured for generations as they have recuperation benefits and are fragrance enhancers. Cultivating these plants is critical to fostering sustainable development since it provides economic advantages, preservation of biodiversity, and health benefits to communities worldwide. The increasing demand for ecological goods and organic components worldwide offers MAPs agriculture tremendous opportunities to contribute to sustainable development. MAPs are rich in metabolites, that are secondary substances generated by plants that have important aromatic and therapeutic qualities. Pharmaceutical, cosmetic, and food sectors all depend on these biologically active compounds, which include alkaloids, flavonoids, terpenoids, and phenolic chemicals. The sustainability of MAPs farming is improved when it is incorporated within a circular economy framework. In order to produce a closed-loop system, a circular economy reduces waste and reuses or recycles resources. This method allows for the repurposing of agricultural by-products produced by MAPs agriculture, such as plant leftovers suitable for composting or bioenergy generation. This lowers waste and increases the effectiveness of resources. Essential oils extracted from these plants significantly enhance the value of raw materials, creating profitable opportunities in the pharmaceutical, cosmetic, and food industries. Sustainable harvesting practices of wild plants and the introduction of cultivation systems are essential for maintaining the balance between conservation and economic benefits. This chapter emphasizes on the importance of growing aromatic and medicinal plants in sustainable development, stressing the importance of agroecological methods, consumer demand, and conservation initiatives that are critical to the industry’s long-term survival while preserving natural resources and promoting economic prosperity.
... 1:10) is reflective of readily available high-CBD cannabis products that are most often used and recommended by dispensaries for use during pregnancy (Dickson et al., 2018;Kuthiala et al., 2022;Mahamad et al., 2020;Sarrafpour et al., 2020;Vastis et al., 2021). Moreover, low ratios of THC:CBD like the one implemented here are often necessary for CBD to have a mitigating effect on the adverse effects of THC (Englund et al., 2023;Pennypacker et al., 2022;Pennypacker and Romero-Sandoval, 2020;Szkudlarek et al., 2019), which is often a motivation for gestational CBD use (De Genna et al., 2023;Sarrafpour et al., 2020). Body weight and food intake of all dams were tracked throughout drug Elevated Plus Maze (EPM). ...
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