101
THC-limits for food: A scientific study
Franjo Grotenhermen, Michael Karus and Daike Lohmeyer
nova-Institute, Hürth, Germany
Introduction
By now, a large number of food items from hemp,
primarily based on hemp seed, is on the market in Europe, the USA, Canada, and
Australia. They include hemp oil, hemp breads and pastries, hemp granola bars,
hemp ice cream with hulled hemp seeds and cider blended with hemp flavored soda
water, to mention just a few.
This recent increase in the use of
hemp seed products for nutrition, and the fact that small quantities of THC may
enter into the food during processing, calls for the expeditious establishment
of a legal framework, specifically a standard for the permissible residual
content of THC (Δ9-tetrahydrocannabinol),
the most relevant psychoactive ingredient of hemp.
The "meat" of hemp seed
itself does not contain any THC. It is primarily found in the flowers and
perigonal bracts surrounding the seeds and, to a lesser extent, in the leaves.
During seed processing, residuals of the flowers may enter the hemp food,
particularly the oil.
Generally, the THC content of hemp
food is so low that psychotropic or even pharmacological effects can be excluded
with certainty, even if larger quantities of food are consumed. Biologically
relevant concentrations of THC were found in hemp oil only in a few isolated
cases. The oil in question was of Swiss origin. It had been pressed from the
improperly cleaned seeds of high-THC varieties, which are legal to grow in
Switzerland. Due to these occurrences, the Swiss government introduced, in 1996,
legal limits for THC in oil and other foods made from hemp seeds.
So far, Switzerland is the only
country worldwide where THC limits for food have been adopted. Two main reasons
call for such action in other countries: The consumer must be able to expect no,
or only insignificant, quantities of THC when consuming food based on hemp
seeds. Not only should psychotropic effects be excluded with certainty, but also
undesired short-term and long-term physiological effects.
The spectre of contamination by THC,
combined with the current un-clear legal situation regarding THC limits, tends
to obstruct the increased use of hemp in food. Only when this matter is settled
will hemp seed and hemp oil achieve the widespread distribution they deserve
based on their nutritional value and flavor. As THC limits in hemp food are
being considered by the authorities in Europe, North America and Australia, it
becomes apparent that a rational and scientifically founded basis for such
limits is still lacking. A detailed study, summarized here, was prepared by the
nova-Institute in order to create such a basis.
Approach
First, our derivation of THC
limits for hemp food required the establishment of maximum single doses, as well
as maximum daily doses, of THC innocuous to health. A safety margin, commonly
used in toxicology, was then applied in order to guarantee sufficient protection
against undesired effects on sensitive people.
To this end, first the placebo limit
for acute psychotropic and physical effects from THC ingestion had to be
determined from the literature. Due its long elimination half-life, THC may
accumulate in the human body. Thus, some researchers have expressed concern that
chronic health effects may arise at THC concentrations in food below the limit
for psychotropic effects. Above all, possible effects on the hormonal system and
fertility, on the immune system, as well as on pregnancy were mentioned. For
that reason, a detailed account of this query is provided. Once safely
permissible oral THC doses were determined, the corresponding maximum
permissible THC concentrations in food had to be derived using consumption
patterns for relevant hemp foods. While typical consumption habits served as a
base-line, the consumption of quantities higher than average had to be
considered
as well. Since hemp-based foods may be consumed in strongly varying quantities,
several categories and their respective limits were established.
Oral dose of THC per kg. body weight |
Description (order of magnitude) |
Maximum plasma concentration |
|
---|---|---|---|
0.014 mg/kg 0.1-0.2 mg/kg 1-2 mg/kg 10-20 mg/kg 100-200 mg/kg |
Recommended
maximum daily dose Placebo limit, psychotropic threshold Heavy Cannabis consumption Medium dose in animal studies High dose in animal studies |
< 1 ng/ml 3-5 ng/ml (15-30 ng/ml ?) 100-150 ng/ml (500-1000 ng/ml ?) |
|
- High dose in cellular studies = 10,000 ng/ml (10 mg/ml). |
Methodological Basis for Determination of THC Limits
Concepts, such as the "lowest
observed adverse effect level" (LOAEL) and the "no observed adverse
effect level" (NOAEL) are commonly applied when developing standards
intended to prevent negative health effects from chemicals which are known, or
suspected, to cause such effects. In order to provide a wide margin of
protection, safety factors of about 10 are usually applied.
The majority of toxicological data
for THC results from animal studies in which high doses were applied, as well as
from cell experimental studies (Table 1). For many of the potential health
effects of THC, the NOAEL was found to range at such high concentrations.
Occurrence of other ad-verse effects at lower dose ranges have also been
discussed. They may be representative of the situation of a chronic heavy Cannabis
consumer (50 to 400 mg of THC per day). Even these doses exceed the threshold
under question, i.e. that for psychotropic effects, by an order of
magnitude. Thus, the available data provide a sound basis for the exclusion for
most of these effects with a high margin of safety.
THC differs from non-specifically
acting harmful chemicals in food in that it acts on compound-specific binding
sites (cannabinoid receptors) on the surface of body cells. However, at high
concentrations, which are not encountered in the case of hemp foods,
non-specific harmful effects, such as direct effects on the cell membrane, are
also observed. The receptor mode of action provides an additional mar-gin of
safety for two reasons:
• As a rule, for most harmful chemicals,
the toxicity increases and the NOAEL correspondingly decreases, with the
duration of exposure. In the case of THC, the opposite applies since its effect
decreases with in-creasing exposure. This is due to the development of a
tolerance to THC by the receptors.
• Children are generally considered
particularly sensitive to various harmful chemicals. Consequently, higher safety
factors are chosen to provide sufficient protection. However, children have a
significantly lower density of cannabinoid receptor sites. Thus, compared to
adults, psychotropic effects occur only at higher THC doses. There are some
non-specific actions of cannabinoids, e.g. some anti-oxidative activity
in doses possibly relevant for the situation of a Cannabis consumer, but
so far there seem to be no relevant harmful non-specific actions in this dose
range.
Biological Basis for Determination of THC Limits
THC is a highly active pharmacological
substance which shows, as a function of dose, effects on a multitude of organic
systems and body functions. The physical toxicity is low, e.g., tests to
establish a lethal THC dose for monkeys have been unsuccessful to date because a
maximum administered dose of 9,000 mg/kg body weight did not result in their
death.
Acute psychotropic effects from the
consumption of products from Cannabis of the drug type, such as marijuana
and hashish, are changes in mood ("high") typical for marijuana, and
changes in the sensory perception, the feeling for elapsed time, etc. Acute
physical effects are, for example, the acceleration of heartbeat and a dry
mouth.
The limit for psychotropic effects is
about 0.2 to 0.3 mg THC (single dose) per kilogram body weight when administered
orally in a lipophilic (oily) matrix. Depending on body weight, this corresponds
to a dose of 10 to 20 mg of THC for an adult person.
An oral single dose of 5 mg THC in a
lipophilic medium is rated as a placebo dose with respect to acute perceptible
psychotropic and physical effects, i.e., it cannot be distinguished from
a placebo. Due to the duration of THC’s effectiveness in therapeutic doses (4
to 12 hours) 5 mg may be taken twice per day, resulting in a NOAEL for acute
perceptible effects of 10 mg THC per day.
In connection with a chronic
consumption of Cannabis for intoxication purposes, the perils of a
possible impairment of the lungs, caused by inhalation of marijuana or hashish
smoke, and the possible chronic effects on the psyche have been discussed. These
effects are of no importance when THC is taken orally in sub-psychotropic doses,
such as with food. While the maximum daily quantity of THC ingested with food
must be safely below the psychotropic threshold, the question of whether
non-perceptible and chronic physical health impairment may occur below the
psychotropic threshold, must also be addressed.
By virtue of the effects observed in
studies relating to animal tests, four areas are of potential interest. They
include effects on the genetic material, on pregnancy, on the hormonal system
and fertility, as well as on the immune system. The available literature
suggests
the following evidence with respect to these effects.
Genetic material: If taken in doses
typical for consumers of marijuana, THC is not mutagenic, not carcinogenic, and
has no effect on cell metabolism. The NOAEL is above the concentrations relevant
to this type of human consumption.
Pregnancy: There are only weak
references to an influence on pregnancy caused by the consumption of marijuana.
Animal studies showed only inconsistent effects, even after the administration
of doses of 10-20 mg THC per kilogram of body weight and more, i.e.,
hundred times higher than those causing psychotropic effects. There have been
reported indications of a slight impairment of the cerebral development of
children of chronic Cannabis consumers, though this could not be
confirmed by other authors. The NOAEL for most parameters related to pregnancy, e.g.,
parturition, duration of pregnancy, infantile abnormalities, weight at birth,
and cerebral development is above the psychotropic threshold and, in most cases,
above the range of chronic marijuana consumers.
Hormonal system and fertility: There
are no consistent findings of THC influence on male and female sex hormones, or
on fertility, caused by the THC intake of regular Cannabis consumers. The
strongest indications of such effects relate to hormonal malfunctions during
puberty and to a temporary influence on the concentration of prolactin and LH in
women during a particular phase of the menstrual cycle. However, these were only
isolated observations. The NOAEL for THC concerning the influence on sex
hormones, other hormonal effects, or other effects relevant to reproduction, are
usually above the range of human marijuana consumption. Again, they are above
the threshold for psychotropic effects.
Immune system: Animal and cellular
studies indicate that THC produces suppressive effects on cellular and humoral
immunity. However, they can be attributed mainly to non-specific toxic effects
and require extremely high doses. In fact, at low doses, various effects
stimulating the immune system or no effects at all were found. The NOAEL for
many relevant parameters relating to the immune system is clearly above levels
relevant to human Cannabis consumption. For some effects, conflicting
observations could be made in the examination of humans and of cells of
marijuana consumers. When such effects were described, they were, even in the
case of a heavy Cannabis consumption, very weak and with a doubtful
relevance to health. The NOAEL for this parameter is, therefore, above the
psychotropic threshold.
Factors reducing the biological efficacy of THC
Since they may strongly affect the
biological efficacy of THC, two aspects have to be considered in connection with
oral THC intake with food:
• THC must be consumed in its phenolic
form in order to be bio-logically effective. However, in unprocessed hemp
plants, THC occurs in the form of its largely ineffective carboxylic acid (THCA).
It is decarboxylated, i.e., converted into its active form, primarily by
heat during baking and other forms of food processing, and when smoked. Thus,
largely unprocessed foods, such as cold-pressed oils, may be permitted to
contain larger fractions of pharmacologically non-efficacious THC carboxylic
acids.
• The degree of THC absorption by the
human intestines also depends on the physical and chemical properties of the
carrier. Generally, lipophilic carriers, such as oils, promote absorption. In
our study, this most un-favorable case, (i.e., maximum absorption of
THC), was assumed for the determination of the maximum daily dose of 10 mg. If
present in less fatty matrices, such as breads, pastries or drinks (hydrophilic
environment), the bioavailability of THC is typically reduced by 50%.
Summary and conclusion on biological effects
The experimental findings summarized
above, suggest a safe maxi-mum THC single dose of 5 mg for a healthy person of
70 kg, corresponding to 70 micrograms per kg body weight (BW). The safe maximum
THC daily dose is 10 mg, or 140 micrograms per kg BW. These doses do not result
in any acute perceptible psychotropic or physical effects nor in any chronic
adverse effects. These doses assume that THC is present in its active, phenolic
form and is taken in a lipophilic basis. If these conditions are not met, the
tolerable dose is higher due to the lower resorption by the intestine and due to
a part of the THC being in the pharmacologically non-available carboxylic form.
The application of a safety factor of
10 results in a tolerable daily dose of 14 micrograms THC/kg body weight or 1
milligram THC for a person of 70 kg. As already mentioned, the assumed safety
factor of 10 represents a conservative choice for two reasons, development of
tolerance despite accumulation of THC and a substantially lower density of
cannabinoid receptors in children compared to adults. Both reduce the potential
for specific psychic and physical effects conveyed by the receptors.
Food | Consumption per year | Consumption per day | |
---|---|---|---|
Oil: Finished products, breads and pastries, non-perishable foods, and pasta: Alcoholic drinks: Nonalcoholic drinks (including herbal teas): |
12 kg 105 kg 170 liters 251 liters |
33 g 288 g 466 ml 688 ml |
Derivation of THC limits
The establishment of a
concentration-based THC limit in food requires that two questions be answered:
• How much THC can be ingested safely
with the diet? This question has been discussed above.
• At what rates may hemp-based foods be
ingested?
Table 2 averages consumption habits
by Germans for market foods which may contain hemp products. The figures are
taken from the data-base of the Federal Statistical Office (Krueger 1998, Weber
1998).
So far, legal THC limits for food
have only been adopted in Switzerland, and only after THC-containing food
resulted in side-effects for some consumers (Table 3).
The Swiss THC limits have proven
their value in practice. On the one hand, producers have been able to comply
with them through proper manufacturing practice. On the other hand, no incidents
of side effects due to the consumption of hemp based food have be-come known
following their adoption.
In 1998, Canada was the second
country to pass THC limits. However, the limit does not refer directly to food,
but to hempen raw and semi-finished products, such as hemp fibers and seeds.
Products containing hemp are exempt from further regulation if they contain less
than 10 milligrams THC per kilogram.
According to the discussion above,
the maximum tolerable daily dose is 1 mg THC (for a person of 70 kg). This dose
includes a safety factor of 10. Table 2 furnishes the data for the average
consumption of food containing THC.
Our recommended THC limits for each
food category can be derived from this data. They are presented in the fourth
column of Table 4. In order to account for potentially higher consumption rates,
the derived limit is multiplied by an additional safety factor which varies for
the different groups of food (see column 3). This additional safety factor also
takes into consideration the potential situation of a person ingesting hemp food
with the maximum permissible THC quantity of all listed groups of food. In the
case of extreme nutritional habits, the safety factor of 10 may be considered
reduced to as little as 5, which is still sufficient due to the low toxicity of
THC. Furthermore, this margin is higher than that for some other natural drug
substances in food, e.g., the quinine, used as an additive in sodas or
alcohol used for embellishment of meat dishes.
A comparison of the nova-recommended
THC limits for food to the Swiss limits suggests the following:
Edible oil: The nova-recommended
limit of 20 mg THC/kg is below the Swiss value of 50 mg THC/kg. The main reason
is the difference in assumed daily consumption of oil (nova-study: 33 g/day,
Switzerland: 10 g/day). This is due to the fact that the nova value includes
edible oils employed by the food industry in processed foods. The additional
safety factor of 1.5 for higher-than-normal consumption is lower than for our
other food categories. This reflects the fact that the food industry rarely
employs oils for food processing which are high in polyunsaturated fatty acids,
such as hemp oil. High-grade oils with intense taste, such as walnut, olive and
hemp oil are mainly used alone, for example as salad oil.
Finished products, breads and
pas-tries, and pasta: The nova-recommended limit of 1.5 mg THC/kg is somewhat
lower than the Swiss limits (2-5 mg THC/kg). Nova took into account more extreme
consumption habits here as well.
Alcoholic drinks: The
nova-re-commended limit is 0.7 mg THC/kg versus the Swiss limit of 0.2 mg
THC/kg. We consider the value of 0.7 mg THC/kg sufficiently low, all the more
since the effect of alcohol, by far, pharmacologically outweighs the effect of
THC. In order to exceed the placebo limit for THC (5 mg), more than 7.0 liters
of alcoholic drinks would have to be consumed.
Nonalcoholic drinks: The
nova-recommended limit of 0.3 mg THC/ kg is similar to the Swiss limit of 0.2 mg
THC/kg. The additional safety factor is higher because particularly large
quantities of nonalcoholic drinks may be consumed without - as in the case of
alcohol - other pharmacological effects dominating.
Considering the conservative nature
of the assumptions underlying nova’s recommended limits, the latter provide
the consumer with a high degree of safety and protection from any acute
perceptible psychotropic and physiological effects, as well as ad-verse chronic
health effects produced by THC. At the same time, the experience of hemp foods
manufacturers in the last few years has shown that these limits can be achieved
through good production practice, without posing an undue burden.
This article is a summary of an
approximately 65 page study by the nova-Institute, providing a detailed
pharmacological and toxicological basis for THC limits for food and extensive
references. Copies are avail-able in German from nova-Institute, Hürth,
Germany, and in English from Hemptech, Sebastopol, California, USA. The English
version is on the Website of the North American Indus-trial Hemp Council (http://www.naihc.org).
The nova-Institute study was made
possible by the kind support from the following individuals and entities (in
alphabetical order). The authors would like to extend their sincerest thanks to
them:
Australian Hemp Resource And
Manufacture, Australia; Dave Pate, International Hemp Association, The
Netherlands; Davert-Mühle Rainer Welke GmbH, Germany; dupetit Natural Products,
Germany; Euro-American Marketing & Promotion Service, The Netherlands;
Genossenschaft Gärtnerei Enetbrugg, Switzerland; HanfDampf Großhandel &
Produktentwicklung, Germany; Hempola, Ontario, Canada; Jace Callaway, University
of Kuopio, Finland; MBR Agrar Service Taunus-Westerwald GmbH, Germany; Mörk
Naturprodukte, Germany; North American Industrial Hemp Council, Wisconsin, USA;
Richard Rose, The Hemp Corporation, California, USA; The Ohio Hempery Inc.,
Ohio, USA; Treuhanf AG, Germany.
Food | Limit mg/kg | Notes | |
---|---|---|---|
Hemp oil Hemp seeds Breads and pastries Vegetable food Spirits Nonalcoholic drinks Alcoholic drinks Herb and fruit teas |
50 20 5 2 5 0.2 0.2 0.2 |
On a dry weight basis On a dry weight basis On a dry weight basis mg per liter of pure alcohol mg per liter of finished products Excluding spirits mg per liter of finished product. Assumes 15 grams of plant parts per kg of boiling water, steeped for 30 minutes above 85ºC. |
Food | Average
consumption per day and per capita |
Additional safety factor |
THC limit (mg/kg) |
|
---|---|---|---|---|
Edible oil: Finished products, breads and pastries, pasta: Alcoholic drinks: Nonalcoholic drinks: |
33 g 288 g 466 ml 688 ml |
1.5 2 3 5 |
20 1.5 0.7 0.3 |
References
Schweizer Bundesamt für Gesundheit [Swiss Federal Health Administration] 1996 and 1998. Lebensmittel-Info, Verwendung von Hanf in Lebensmitteln und Gebrauchs-gegenständen, Kreisschreiben Nr. 2 from 13.3.1996. Fremd und Inhaltsstoffverordnung, FIV (AS 1998): Liste der zugelassenen Höchstkonzentrationen (Toleranz- und Grenzwerte) für andere Fremdstoffe oder Inhaltsstoffe [Use of hemp in foods and utility items, list of acceptable maximum concentrations for ingredients].
Mr. Krüger 1998. Personal communication on June 8 and 16 (Federal Office for Statistics, Berlin, Germany).