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The vaporisation of cannabinoids heating plant matter or pure compounds to a temperature where active cannabinoid vapours form but below the point of combustion is a safe method of intrapulmonary administration because it avoids risks associated with smoking and the formation of pyrolytic toxic compounds as a result of combustion [ 11 ].
While some studies have reported on the effects of vaporised THC e. Oral dosing with CBD impedes the potential to examine its interactive effects with THC when the two compounds are administered simultaneously, a scenario with ecological validity for understanding effects in recreational and medicinal cannabis users.
Alternative routes of administration of CBD with rapid action, such as vaporisation, would also benefit further investigations of its therapeutic potential as an anxiolytic or antipsychotic, among other applications.
The purpose of this article is to describe methodology developed for the administration of THC alone, CBD alone and their co-administration by means of a vaporiser for studies of acute cannabinoid effects in humans. Since the therapeutic anxiolytic and antipsychotic doses of orally administered CBD have generally been quite high e.
Tuttlingen, Germany and was used according to the manual as provided by the manufacturer. Before each new experiment the filling chamber was thoroughly cleaned with ethanol and allowed to dry at ambient temperature.
A new liquid pad was used for each experiment. For each experiment, the filling chamber fitted with a loaded liquid pad was placed onto the vaporiser stabilised at the desired temperature. The balloon was then immediately attached and the ventilation was started. Finally the solution was filtered through a 0. Recovery from the filter was found to be The software used was Chemstation Rev. The HPLC method used was previously described [ 11 ]; adapted in [ 17 ] and validated again here.
The method was validated for linearity, accuracy, precision, and limit of quantification LOQ. To establish the linearity of the method, 6-point calibration curves were prepared for THC and for CBD in the range of 0. Intraday precision was calculated by analysing all analyte samples three different times in a day.
The same procedure was followed for four different days to determine interday precision. The method showed excellent validation results, with an average linearity of 0. Intraday precision was 2. A series of preliminary experiments was conducted first to determine optimum forms of CBD for vaporisation crystalline versus ethanolic solution , maximum volumes of ethanolic solution that could be held by the liquid pad, and hence maximum doses that could be achieved.
The quantity of cannabinoids delivered into each balloon and the residue remaining on the liquid pad were quantified by HPLC. Solubility concerns for CBD in ethanolic solution and anticipated inability of the liquid pad to hold the large quantities of liquid, led to preliminary testing using CBD in crystalline form.
Finally, we proceeded to establish whether CBD in ethanolic solution of similar concentration would vaporise similarly to what we had established for crystalline CBD [Pilot study 4; see Additional file 1 ].
This was deemed to be particularly pertinent since pure THC is generally vaporised dissolved in ethanol and it would be desirable for randomised administration studies of both compounds to humans to deliver each compound similarly, and enable ethanol to be used in a placebo condition.
This series of preliminary studies was used to determine the optimum dose delivery and vaporisation protocols for planned use in a randomised controlled trial RCT of cannabinoid THC and CBD administration to humans [ 18 ]. Having identified a range of properties pertinent to optimising vaporisation of CBD, we then selected specific doses for confirmation and replication toward the planned RCT.
This was designed to achieve clinically relevant intoxication without significant adverse effects. CBD ratio that had been more common in street level cannabis products although highly variable [ 19 , 20 ].
All experiments used a normal size balloon and each experiment was performed in triplicate i. A decision was made to continue experiments with the normal size balloon for its greater ease shorter duration of inhalation for the participants in the planned RCT [ 18 ].
This was performed in order to determine whether a second balloon could be administered to participants with additional THC to equalise the quantity of THC delivered when in combination with high dose CBD, to that when administered alone. Again the quantity of THC delivered into the balloon was approximately halved: Experiments 5 and 6 indicated that a saturation effect in the vapour may occur when the two compounds are vaporised together at high CBD doses but not at low CBD doses as in Experiment 3.
Data represent averages across three repetitions; error bars are SEM. To our knowledge, this is the first reported methodological study toward intrapulmonary administration of CBD alone and in combination with THC in the literature. Vaporisation provides a safe and efficient delivery system for cannabis and cannabinoid compounds, avoiding the respiratory toxins inherent in smoking, making it useful for clinical trials.
The rapid delivery into the bloodstream producing immediate effects made possible by this method of administration may benefit in particular human research studies that have to date relied on oral administration of CBD, with its delayed onset of effects and inherent problems regarding bioavailability and liver metabolism.
Benefits may also extend to research toward further development of CBD for therapeutic use for a range of indications and disorders including amongst others, schizophrenia [ 3 ] and anxiety disorders [ 21 ].
Administration of THC and CBD together mimics the natural constituency of cannabis plant matter, prior to the more recent selective breeding that has resulted in the reduction or even elimination of CBD while maximising THC content [ 20 ], and the methods described here can assist with enabling researchers to examine the effects of the two compounds delivered simultaneously. The ability to do this by vaporisation overrides the necessity to pre-dose with oral CBD hours prior to the administration of inhaled THC, which in itself results in altered pharmacokinetics and pharmacodynamics [ 22 ] but see also [ 23 , 24 ] , and provides for the development of a better understanding of the interaction between the two compounds, enabling well-designed experiments of dose-dependent effects.
The experiments performed in triplicate here determined the doses that could be achieved in our own RCT as follows to demonstrate the application of the protocols we report here [ 18 ]. Where only ethanol was administered, the ethanol vapours were blown off as described above, such that only mildly ethanol vapour flavoured air was delivered. The results of the experiments reported here determined that the quantities of cannabinoids actually delivered via vaporisation would be comparable across the primary conditions of interest: A limitation of this methodological report is that it has focused entirely on the technical aspects of feasibility of vaporisation of CBD alone and in combination with THC.
The work reported here is the necessary first step for any further studies of this type with human subjects. Further limitations to consider with the vaporisation route of administration are that despite attempts to adhere to controlled breath holding, there may be variability in absorption related to the depth of respiration, individual patterns of breathing and coughing, as well as the variable size of particles in the vapour adhering at differing points within the respiratory system e.
The presence of both compounds reduces the delivery of each when the dose of CBD is high, likely due to saturation effects in the vapour.
Further adjustments could potentially be made to vaporisation protocols and the doses loaded to try to better achieve the desired dose delivered. For example, we opted to have participants inhale two standard size balloons to maximise the dose of CBD delivered, judging it to be impracticable to have participants inhale two XL size balloons because of their large volume and the time restraints and other demands on participants in our RCT ; for other experiments researchers may opt to use one or two XL size balloons and achieve greater dosing by this means, with less wastage of the CBD dose loaded.
The total doses delivered from these two balloons equal 6. Alternatively, THC and CBD could be loaded and vaporised separately into two balloons that the participant inhales sequentially, but this could result in quite different pharmacokinetic and pharmacodynamic effects compared to simultaneous administration of the two compounds and the methodology depends upon the questions to be addressed in the research.
Many questions arise regarding additive, synergistic and interactive effects of THC and CBD and the field is ripe for the further investigation of these intriguing compounds. The methods, protocols and preliminary data presented here established the optimal efficiency of delivery of both low and high doses of CBD, alone and in combination with THC, by vaporisation. The studies informed the development of methods for a randomised controlled trial of simultaneous acute administration of these cannabinoids by vaporisation to human research participants in our laboratory [ 18 ], and may assist researchers with designing their own future clinical trials and experimental human studies a.
CBD when vaporised produces dense vapour that is irritating to the throat for some participants and generates sometimes significant coughing. We have facilitated the comfort of participants inhaling CBD vapours by offering small sips of water or juice, ice or sweets to suck and soothe the irritation, or sometimes unmedicated cough lozenges.
It is recommended for blinding purposes to mask these differences by covering the balloon e. All authors declare that they have no competing interests. CB1 receptors are found mainly in the brain but also in the liver, kidneys, and lungs , while CB2 receptors are found mainly in the immune system. As we discussed above, there are several types of cannabinoids. Even within phytocannabinoids, there are wide ranges of compounds and effects that we are still learning about.
Other cannabinoids, like CBD, have fewer direct effects on the endocannabinoid system keep this in mind as you read the next section. Cannabinoids represent a diverse class of chemical compounds that can be very different from each other. For example, arachidonoylethanolamine AEA is produced within the body and is thought to regulate several functions. For example, CB1 receptors send signals that regulate senses, while cannabinoids that interact with CB2 receptors can at the same time affect gastrointestinal response and peripheral nervous system sensitivity.
Also, since people often take numerous different cannabinoids together for example, using medical marijuana , it is hard to attribute specific effects to specific cannabinoids. In addition, some cannabinoids interact synergistically, producing unique effects that are not found when using them individually. However, CBD does this and produces many other effects without directly interacting with the cannabinoid receptors. At first, scientists thought there was a third type of CB receptor just for Cannabidiol, but the answer was far more interesting and revealing.
The indirect interactions of CBD with the endocannabinoid system has many effects, some of which surprised scientists and are still being researched. However, scientists are still unclear about how some effects of Cannabidiol are actually occurring. The most possible explanation is via the hypothetical GPR55 receptor, or through more indirect and synergistic effects that still await discovery. Contrary to how most cannabinoids function, CBD interacts very mildly with the cannabinoid receptors themselves and instead either helps other cannabinoids to be better absorbed or stops the effects of whatever makes the receptors work less effectively.
The endocannabinoid system is closely interconnected with the nervous and immune system. You may have heard some people say that marijuana and hemp are exactly the same, while others swear they are different. The debate of hemp vs marijuana is fueled by the confusion and misinformation that surround the cannabis plant. In this article, we will dispel several myths and shed light on the differences between industrial hemp and marijuana. As you may know, industrial hemp and marijuana come from the same genus of flowering plant— cannabis.
This means that there may be multiple types of the cannabis plant, which are all cannabis but have remarkable differences. Cannabis sativa is the most common strain of cannabis. It has been cultivated throughout history for a number of purposes, including the production of seed oil, food, hemp fiber for clothes and rope , medicine, and even recreation.
Cannabis ruderalis is a species native to Russia that flowers earlier and is able to withstand harsher conditions than Cannabis sativa and Cannabis indica. It is the hardiest of the three, but it is relatively poor in terms of cannabinoids as ruderalis has a lower THC content than either sativa or indica. Cannabis indica was first discovered in India and is a cannabis species that is described as shorter and bushier than sativa.
Problems with botanical taxonomy have led some scientists to still doubt the existence of Cannabis indica as a distinct species of cannabis. However, since man has been cultivating cannabis and especially Cannabis sativa for thousands of years, the effects of artificial selections have led to several different types of cannabis even within the same species, depending on the purpose the cannabis was cultivated for. Cannabis has been cultivated by humans, for a variety of purposes, since antiquity.
So it comes as no surprise that there are several different species and even different varieties within the species, depending on the purpose the plants were bred for. Through artificial selection, different species of cannabis have different properties—some have been used for medicinal purposes, others as food, and others to create clothes, ropes, and other items. Industrial hemp is produced by strains of Cannabis sativa that have been cultivated to produce minimal levels of THC and are instead artificially selected and bred to grow taller and sturdier.
This is done to enable the plant to be used effectively in the production of hemp oil, wax, resin, hemp seed food, animal feed, fuel, cloth, rope, and more. Industrial hemp is exclusively made from Cannabis sativa. Medical marijuana is produced mainly from variants of Cannabis sativa that have been selectively bred to maximize their concentration in cannabinoids.
Cannabis ruderalis is almost exclusively grown due to its naturally occurring very small quantities of THC. The major and arguably the only difference between industrial hemp and medical marijuana is that industrial hemp is exclusively made from Cannabis sativa that was specifically bred to produce the lowest concentrations of THC possible.
Hemp-producing cannabis has tall, fibrous stalks that are very strong and have very few flowering buds. On the on the other hand, marijuana strains are short, bushy, and have high amounts of THC.
Since industrial hemp is naturally rich in CBD and has been bred to have only trace amounts of THC, many people today are turning to industrial hemp products as an alternative to medical marijuana. Medical marijuana is not legal in all states in the US and many countries worldwide, while products made from industrial hemp can be a safe and legal alternative.
Industrial hemp products are completely safe, as they are made according to federal standards and are produced in FDA-registered facilities within the US. Most of our readers know you can get Cannabidiol CBD products made from industrial hemp. Many of you also know that you can get CBD products from medical marijuana.
Yes, medical marijuana can contain any level of THC whereas CBD products from industrial hemp contain negligible amounts. But what about the CBD? In regards to its chemical composition, which is precisely known to scientists, CBD remains unchanged regardless of which plant produces it. There is no room for different interpretations and the substance is just that.
This is pure chemistry and allows no room for ambiguity. However, the main question people have is not just about the CBD compound, which is constant from plant to plant, but the actual difference in CBD oil from various plants. The production of hemp oil involves extracting the fatty acids from the stalks of the cannabis plant.
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