The Title of this publication as "Drug Injury", allows a wide range of sub-topics and an almost endless level of health related information. Thus, the inclusion of this Chapter is a de facto statement that Marijuana/Cannabinoids are an integral part of our Drug Lexicon. Historically, the Medical/Drug aspect of Marijuana is well documented in the On-Line entity at ProCon.org as recently as 08/13/2013. And, lest the reader retain some skepticism as to the Drug categorization of Marijuana/Cannabinoids, our U.S. Government was issued a Patent # 6630507 in Oct. 2003 for Marinol. This synthetic Cannabinoid Drug had a recommendation as "cannabinoids as antioxidants and neuroprotectants". This Patent stands not withstanding the statement of "no medical use" for Marijuana in the 1970 placement as a Schedule 1 substance in the Controlled Substance Act. And, even more incredulous, given the 1937 Marijuana Stamp Act that established Marijuana as an Illegal Substance.

Perhaps having learned the lessons of Alcohol Prohibition with the consequent establishment of Domestic Crime Families, and, the War On Drugs with the establishment of Foreign Drug Cartels, our U.S. Government created the "Pot Farm" in Mississippi in 1969. That University-based facility produces Marijuana Cigarettes allegedly to this day for at least one smoker in Florida. The "Farm" initially also afforded material for researchers at Research Triangle Park in North Carolina for groundbreaking research by Dr. Wall, et al., on the Pharmacokinetic and Pharmacodynamic aspects of Marijuana/Cannabinoids. That New Beginning of research studies on Marijuana was then turned Clinical with the National Cancer Institute studies in 1980; but even more so after the New Mexico Legislature in 1978 concluded that Marijuana has Medicinal Value.

To recapitulate briefly, I note that the U.S. Government had/has Marijuana as an "illegal substance"; being grown for distribution to individuals and Institutions; which has "no medical use"; which has/had a Patent with health recommendations. These apparent internal Governmental inconsistencies are matched by the overarching competing Societal efforts. Thus, we have over 20 National Political entities (States) with Medical Marijuana Facilities; we have a West Coast block of 4 States with, or, soon to have recreational Marijuana use; we have Official Marijuana growers, and, unofficial growers. The topic of Marijuana may be a classic case of States'Rights v. Federal Duties v. Personal Freedoms. This truly Democratic Conundrum was recently documented In "Medicolegal Aspects of Marijuana Colorado Edition" from Lawyers and Judges Pub. Co, 2015.

As noted in the foregoing, as well as well documented in the general press, and On-Line outlets, Marijuana and the derived Cannabinoids have moved to straddle the fence/divide/chasm between Prescription Drugs, and, Drugs of Abuse. These Individual, State, and, Federal Efforts toward effective movement of Marijuana related products as available for the Common Good is now about 50 years young. And, given the recent pace of change in Society and Legislatures, Marijuana is moving to be a commercially marketed Integral part of our Societal Spectrum of Substances of Abuse which include Alcohol, Tobacco Products, Foods, and Prescription Drugs.

Now, given that Marijuana and related Cannabinoids are variously still on the Illegal/Legal fence in some sections of the U.S., the following presentations evaluate Smoking, and, Ingestion as routes of assimilation of Marijuana related products. It is anticipated that this afforded level of Information will prepare the Patient, and, Recreational User as to expectations which are the Marijuana Experience.

Synopsis
12.1 Cannabinoid positive: After Smoking

1. Introductory Summary
2. Questions in Search of Answers
3. Scientific Data Relating to THC
1. Blood THC v. brain THC: any relationships?
2. Relationships between percent plant-THC and plasma-THC
3. Relation between degree of "High" and plasma-THC
4. Occasional marijuana users v. practiced users
5. Is THC the only psycho-active cannabinoid
6. Urine testing for cannabinoids: clinical or evidentiary value?
7. Impairment & marijuana: laboratory and on-road data
4. Conclusions

12.2 Under the Influence: After Ingestion

1. Introductory Summary
2. Some Comparative Data On Smoking And Ingesting Cannabis:
1. How do bioavailability measures relate to Ingestion?
2. Is Dronabinol administration a good model for cannabis Ingestion?
3. Any overall advantages of the oromucosal route?
4. Can the effects after ingestion of cannabis be made more objective?
3. Conclussions
   Endnotes

12.1 Cannabinoid Disposition: After Smoking

A. Introductory Summary

In the 20 years from about 1993 until 2013, the marijuana testing program at the University of Mississippi has demonstrated that the average THC(Tetrahydrocannabinol) concentration of the generally available marijuana has increased from about 3.1 percent.¹ Recent testing has shown average values between 25 and 28 percent, and values of 36-40 percent THC. Also, during about the time frame since the 1970s, some states have decriminalized marijuana possession, and about 20 states and the District of Columbia have permitted the dispensing of medical marijuana.^2,3 Thus, we now have hundreds of sources of marijuana on the "street," and such clinics and dispensaries compete with the unregulated marijuana sources. Furthermore, both Colorado and Washington have legalized recreational marijuana. This broadening of the market for marijuana use may increase the number of users.

The challenge of this new and possibly increasing prevalence of marijuana use requires effective evaluation by businesses, governments, legal entities, and scientists to position marijuana use into a positive functional societal role. Thus, the authors having expertise as small businesses, laboratory scientists, and consultants, afford this brief review of some of the scientific studies in the marijuana arena. In so doing, we evaluate the logic of a five nanograms per milliliter (ng/mL) level of blood THC in assessing the psychomotor functionality of a marijuana user when, in fact, the marijuana smoker attains a plasma THC level up to about 250 ng/mL that decreases to less than ten ng/mL in the one hour from the beginning of a ten to 15 minute smoking session. Even more confounding are the results of two seven-day abstinence studies in which THC-positive plasma test results even after the seven-day washout period show THC up to 5.5 ng/mL.^4,5 Even more absurd is the 2006 report which recommended a THC level of 0.5 ng/mL as the cut-off for psychomotor functionality.⁶ We thus propose, based upon the following, a plasma THC level of 30 ng/mL as an objective value toward assessing impairment related to marijuana smoking in accident/incident conditions.

B. Questions in Search of Answers

1. Blood THC v. brain THC: Any relationships?
2. How does the percent THC in the smoked marijuana cigarette relate to blood levels of THC in the user?
3. How does the blood level of THC relate to the perception of "high" in the user?
4. Is the practiced/heavy marijuana user just one end of the scale for dose-response effects?
5. Is the blood level of THC the only cannabinoid¹ of interest in evaluating behavioral effects in the user?
6. Is urine testing for cannabinoids of any either clinical or evidentiary value?
7. Impairment & marijuana: laboratory and on-road considerations.

C. Scientific Data Relating to THC

1. Blood THC v. brain THC: any relationships?

Given that the use of marijuana is fostered by the effects of the cannabinoids upon the brain of the smoker, it is appropriate that some early studies attempted to measure the concentrations of cannabinoids in the brain.^7,8,9 Animals were of necessity in those quantitative studies, such as mice, rats, and pigs, which afforded consistent comparable results. Thus, a 1972 study with radioactive THC found brain levels were at their maximum 15 minutes after intravenous administration.⁷ The noted two cannabinoids were THC and Hydroxy-THC, and the effects paralleled the brain cannabinoid levels over 1.5 to four hours.¹⁰ A similar study with mice noted relative cannabinoid levels in the smoke were the same as relative levels in the brain for three Cannabinoids.¹¹ They further showed that no Hydroxy-THC was in the smoke condensate, but was found in the brain. Other studies have proposed that THC is metabolized in the lung and liver but no definitive data is available as to metabolism in either brain tissue or brain blood vessels. The evidence is that both THC and Hydroxy-THC easily penetrate into brain tissue, with Hydroxy-THC most easily accumulating in the brain. Likewise, a study with eight cannabinoids noted that all showed effects correlated with their brain/plasma level ratios.⁹

2. Relationships between percent plant-THC and plasma-THC

As noted in the foregoing, the THC in available marijuana can be as high as 36 percent. However, the science is a bit behind these numbers in that most of the available studies are with marijuana in the range from 1.3 to about 13 percent THC per cigarette. Moreover, the free molecules of THC in the marijuana plant are not the defining number as to the potential blood level of THC in the user. New molecules of THC are created during smoking, while some THC is destroyed during smoking.¹² Thus, only ten to perhaps 60 percent of the potential THC in the plant is actually delivered to the user. Further of note is the use of the word "blood" in some of the studies. Blood is normally used to denote whole blood, rather than the derived fractions known as plasma and serum. And, given that plasma is about 55 percent of the whole blood and THC, and other cannabinoids are about 90 percent bound to proteins in the plasma, the specimen of choice for marijuana studies is plasma from the living humans.¹³

Now, following up on the question, "is there a relationship between percent THC in the smoked cigarette and plasma THC?" the following edited tabulation from two articles in 1990 and 2006 allows an initial answer.^14,15

Just looking at the numbers in the two columns of plasma levels, there seems to be no direct relationship of increasing levels with increasing the percent of THC. In fact, the average value for the maxima of the ranges is 171.8 with a standard deviation of 44.3. That is only a variation of 26 percent in the high plasma levels for about a 1,200 percent increase in the plant-THC level. A similar evaluation of the column of "Ave. Plasma THC" data affords an average value of 109.02 +- 31.5 with a Standard Error of 29 %. Clearly, there is no relationship between the dose (amount of THC) and one's response (which is the plasma level of THC). The true variable herein is likely the user, whereby a level of effect is personally attained by adjustments in smoking to obviate the variable amount of THC in the cigarette.¹⁶ A next logical conclusion could be that even with marijuana at 25 percent THC or higher, users will not increase their maximum plasma THC levels. In fact with more THC per puff, one could expect total smoking will not increase.

3. Relation between degree of "High" and plasma THC

One learns to smoke, and to get to a "high" that is likely unique to the person as suggested in the above data analysis. And, as suggested in the following tabulation, with no dose-response relationship, some persons report a perception of a "high" from marijuana cigarettes with little-to-no THC.¹⁷ The "personalization" of this phenomenon, "the high," seems to be well illustrated in the following tabulation.^11,12,18,20

An analysis of the tabulated results above allows one to conclude as per the previous tabulation of percent plant THC v. plasma THC, that there is no direct relationship between the degree of "high" and plasma THC level. In addition, an analysis of the range of the maxima for the range of plasma levels, affords an average of 214.1 with a Standard Deviation of 55.9. Again, similarly as for the percent THC, we note only a variation of 26 percent when the "degree of high" changed by more than 1,000 percent. Thus, the first entry in the table shows that the "high" was experienced by no one, even at a plasma level of 190, and, some noted a maximum "high" of ten with a Plasma THC of only five. Once again, it seems that the true variable is the user.

As reported by Heustis, et al., the peak plasma level can occur in five minutes while smoking, or up to about 15 minutes post smoking even after the intravenous administration of THC.¹⁸ And, the peak level is usually found before the perception of the "high." It has also been shown by Heustis, et al., that the plasma level of THC decreased from about 150 ng/mL to less than ten ng/mL within about 50 minutes after starting to smoke.¹⁹ Moreover, the practiced user will usually experience the "high" earlier than the occasional user under the same conditions, as does the alcohol drinker at low blood alcohol levels.²⁰

4. Occasional marijuana users v. practiced users

As noted in the foregoing, the practiced marijuana user is additionally distinguishable from the occasional user by at least the following...Continue to read rest of article (PDF).