Cbd oil for captive gorillas
A Critique of a Controversial Study on THC Effects in Primates A Report from The Society for Neuroscience Annual Meeting – New Orleans, LA, Nov. 4-8, 2000
A Critique of a Controversial Study on THC Effects in Primates
By James Stewart Campbell, M.D. ([email protected])
At this huge meeting, where over 25,000 neuroscientists from all over the world gathered to trade information on all facets of brain research, there appeared only one study on the effect of delta-9-tetrahydrocannabinol (THC) in primates. There were no studies in humans. Two other studies in rats or mice showed interaction of THC with nicotine and opiates, but these animals were given a THC-per-weight dose approximately 1000 times that of primates, so the models must be viewed with that massive dose in mind, and thus are not reviewed in this report.
The primate study, funded by the U.S. National Institute for Drug Abuse (NIDA) and carried out by S.R. Goldberg, P. Munzar, and G. Tandra, was entitled “Self administration behavior maintained by delta-9-tetrahydrocannabinol, the psychoactive ingredient of marijuana in squirrel monkeys.” It should be noted that the lead author, Dr. Goldberg, works at the Preclinical Pharmacology Section of NIDA in Baltimore, MD. Dr. Goldberg was present at the report at a poster session presentation on Sunday, November 5, and responded to my questions and provided a copy of the poster.
In essence, a small number of squirrel monkeys (the number is not specified in the poster, but 4 animals are identified in graph labels) were first taught to self-administer intravenous cocaine by pressing a lever when a light came on (a fixed-ratio reinforcement schedule). This step was necessary because numerous attempts over the past 30 years to get any animal to selfadminister THC have been unsuccessful. Training occurred in one-hour experimental “sessions” conducted daily on weekdays. Once accustomed to getting the cocaine, this response was “extincted” by not giving the cocaine after the lever press until the monkeys only pressed the lever a tenth as much as when the cocaine was given. Just how long this extinction took is not reported, but it was more than 3 sessions, according to graphical data. Then THC doses reportedly comparable to that received by smoking a reasonable amount of marijuana (1 to 8 micrograms per kg, I.V.) were given in response to a lever press, using a second-order reinforcement protocol. The monkeys quickly learned over 1 to 3 sessions to press the lever to get this “reward.” In short, they seemed to like the effects, at least up to a point. Careful observation of the graphical data indicated that up to 4 μg/kg per dose, the animals pressed the lever more frequently. At 8 μg/kg doses, however, there was a distinct and highly significant reduction in lever presses to the level of half that found with 4 μg/kg. No explanation was given for this finding, and it was not mentioned in the study results or conclusions. The experiment also included sessions after pre-administration of SR141716A, a drug which seems to block the effects of THC, but not cocaine. On this regimen, the monkeys reduced their lever pressings to the extinction point in three days, recovering the lever press frequency to THC 2 to 3 sessions after the blocking agent was stopped. No effect of SR141716A was seen in sessions where cocaine was the test drug.
Official Study Conclusions
The six conclusions reached by the study authors were as follows:
1) “The active principle in cannabis, THC, possesses strong reinforcing properties in experimental animals, in this case, non-human primates, as it does in human subjects.”
2) “The findings further suggest that marijuana has as much potential for abuse as other drugs of abuse, such as cocaine and heroin.”
3) “The selective reduction of THC but not cocaine selfadministration by SR141716A indicates that this abuse potential is likely mediated by cannabinoid CB1 receptors in the brain.”
4) “THC self-administration by squirrel monkeys was obtained using a range of doses in agreement with the total intake and the single doses self-administered by humans smoking marijuana cigarettes.”
5) “The recent discovery of new therapeutic actions of marijuana has increased public debate on the legalization of smoked marijuana as a medication. The present findings of persistent, reliable self-administration behavior with marijuana’s psychoactive ingredient, THC, should help to better inform this debate.”
6) “This methodology provides an exciting opportunity to study neuropharmacological mechanisms underlying marijuana abuse and to develop drugs possessing therapeutic efficacy similar to or better than marijuana or THC but lacking the potential for abuse.”
The Conclusions as Seen by This Observer (JSC)
The above six conclusions as rewritten after careful study of the poster:
1) Once cage-raised, chair-restrained squirrel monkeys are habituated to self-administering intravenous cocaine as a “drug of entry”, they tend to self-administer intravenous THC under similar conditions. Any extension of this conclusion to non-primates, or other primates, including humans, cannot be made by this study.
2) No conclusion as to the abuse potential of THC in squirrel monkeys or any other species can be drawn from this limited study. However, the finding that higher doses of THC reduce the self-administration rate in these monkeys indicats that there is a self-limiting “ceiling” to the self-administration of THC in this species.
3) SR141716A blocks the self-administration of THC in squirrel monkeys previously habituated to cocaine self-administration. Where and how this action takes place cannot be drawn from this study.
4) Intravenous THC self-administration by squirrel monkeys habituated to cocaine seems to occur only at a dosage range similar to the dosage range of respiratory self-administration of THC-containing smoke in humans.
5) The present limited findings of selfadministration behavior with marijuana’s psychoactive ingredient, THC, may prove to be valuable concerning public debate on the legalization of smoked marijuana as a medication. But these findings should not be unduly extended or even be found to be reliable until verified in independent laboratory experiments.
6) This methodology may provide an opportunity to study neuropharmacological mechanisms underlying marijuana self-administration by cage-raised monkeys and to screen drugs possessing therapeutic efficacy similar to or better than marijuana or THC but lacking the potential for self-administration by these monkeys.
Discussion This particular study is important in that it shows how strongly the sponsor of a scientific study affects the conclusions drawn from the work. In this case, Drs. Goldberg, et. al, performed a fairly rigorous scientific investigation, then apparently embellished the report to satisfy NIDA official policy. This bias is shown from the first sentence of the poster, which reads: “Marijuana is among the most abused illicit drugs in the world.” Note the NIDA-inspired keywords – “abused,” “illicit,” and even “drugs.” The authors simply could not write “Marijuana is among the most used psychoactive agents in the world” without putting their funding, careers, and livelihood in jeopardy. This is the cloud under which NIDA scientists must function if they are to survive. When I brought this up to Dr. Goldberg at the meeting, he at first denied that he could lose his job because he was tenured. But he did not deny that he worked independently of outside influence. After all, tenure means little today when administrators can assign you to a small windowless office in the basement and deny funding for your work.
Accordingly, the authors’ conclusions are grossly tainted by this bias, as exampled by the two comparative sets of conclusions shown above. Extending the “strong reinforcing properties” of cannabis to humans in the first conclusion is an example. There weren’t any humans in the study! How can this then be a scientific conclusion? What has been shown in the study is that a handful of chronically bored and possibly depressed cage-raised and restrained squirrel monkeys that have been specially taught to self-administer IV cocaine will also self-administer IV THC. This is the first time any animal has been taught to self-administer THC under any conditions. To extend this very limited result to include human behavior is grossly unscientific.
Furthermore, any researcher worth his grant money should have noticed the ceiling effect of reasonable THC doses in these monkeys. These captive and drug-trained monkeys liked THC, but only in a very limited way. Why did they reduce lever pressing at the higher dose of THC? Were they “stoned” and passive or drifting off? This is not mentioned in the poster. Perhaps this is the well-known ceiling effect of THC (seen in humans) that was not recognized as a worthwhile finding, as it indicates that THC self-administration has intrinsic limits that are far short of the toxic dose of THC. But why labor over the “NIDA-Speak” in the study poster at all? One seasoned neurophysiologist remarked that he always ignores the obvious propaganda-laced conclusions, and goes right to the graphs and technical data to find what really occurred in NIDA studies. That may be fine if one is a neuroscientist, but politicians may read only the conclusions and rush to legislate public policy with drastic results. Indeed, Dr. Goldberg proudly told me that the conclusions of this study had already been influential in the recent British debate in parliament where the conservatives had insisted on draconian penalties for simple marijuana possession. The “addictive” properties of THC shown by this study had been one of the main arguments for the increased penalties.
Happy birthday to Colo: Oldest gorilla in US turns 60
COLUMBUS, Ohio (AP) — She is a mother of three, grandmother of 16, great-grandmother of 12 and great-great-grandmother of three. She recently had surgery to remove a malignant tumor, but doctors say she’s doing well.
She’s Colo, the nation’s oldest living gorilla, and she turned 60 on Thursday at the Columbus Zoo and Aquarium.
Colo was the first gorilla in the world born in a zoo and has surpassed the usual life expectancy of captive gorillas by two decades. Her longevity is putting a spotlight on the medical care, nutrition and up-to-date therapeutic techniques that are helping lengthen zoo animals’ lives.
“Colo just epitomizes the advances that zoos have made, going all the way back to her birth at Columbus,” said Dr. Tom Meehan, vice president for veterinary services at Chicago’s Brookfield Zoo and veterinary adviser to a national gorilla species survival plan.
The changes also mean more animals living with the normal aches and pains of growing older. Today, zoo veterinarians regularly treat animals for heart and kidney disease, arthritis, dental problems and cancer.
Hundreds of people gathered at the zoo Thursday to see Colo, singing “Happy Birthday” moments before the gorilla ambled into an enclosure decorated with multicolored construction paper chains and filled with cakes such as squash and beet and cornbread with mashed potato parsley frosting.
Among the first in line was Pam Schlereth of Columbus, who at 63 was just a little girl when her father brought her to see the newborn Colo in a gorilla incubator in 1956.
“It’s a tribute to the zoo that she’s alive at 60 years old,” Schlereth said.
Colo represents so much to the zoo, Tom Stalf, president of the zoo, told the crowd. “It’s all about connecting people and wildlife,” he said.
Colo is one of several elderly gorillas around the country. The oldest known living male gorilla, Ozzie, is 55 years old and lives at the Atlanta Zoo, which has a geriatric gorilla specialty.
At Seattle’s Woodland Park Zoo, staff members use acupuncture, massage, laser therapy, and heat and joint supplements to help Emma, a 13-year-old rabbit.
At the National Zoo in Washington, Shanthi, a 42-year-old Asian elephant with arthritis, receives osteoarthritis therapy and was recently fitted with specially crafted front foot boots to help her feet heal as medications are applied.
In Oakland, California, Tiki, a 27-year-old giraffe and one of the oldest in the nation, gets foot care, massage therapy, acupuncture and chiropractic care, along with traditional veterinary medicine. Gao Gao, a 26-year-old male panda at the San Diego Zoo with a heart condition, periodically undergoes cardiac ultrasounds.
“Geriatrics is probably one of our most common medical challenges that we face in a zoo situation,” said Dr. Keith Hinshaw, director of animal health at the Philadelphia Zoo. “So pretty much anything that you could imagine would happen with an older person is going to happen eventually with any animal.”
That’s up to and including medication: JJ, a 45-year-old orangutan at the Toledo Zoo, is on the human heart medicines carvedilol and Lisinopril, along with pain and orthopedic medications. He also takes Metamucil.
Colo, a western lowland gorilla, holds several other records. On her 56th birthday in 2012, she exceeded the record for longest-lived gorilla. On Thursday, she surpasses the median life expectancy for female gorillas in human care (37.5 years) by more than two decades.
Other age-defying zoo animals:
Coldilocks, a 36-year-old polar bear at the Philadelphia Zoo and considered the oldest polar bear in the U.S. The bears’ typical lifespan in captivity is 23 years. The zoo says treating her early for kidney disease appears to have helped prolong her life.
Elly, an eastern black rhino at the San Francisco Zoo estimated to be 46 years old, is the oldest of her species in North America. She has had 14 calves, and her offspring have produced 15 grandchildren, 6 great-grandchildren and 1 great-great-grandchild.
Packy, an Asian elephant at the Oregon Zoo, and at 54, the oldest male of his species in North America. The zoo says Packy, born in 1962, became the first elephant to be born in the Western Hemisphere in 44 years.
Nikko, a 33-year-old snow monkey at the Minnesota Zoo, the oldest male snow monkey in North America.
Little Mama, a chimpanzee living at Lion Country Safari in Loxahatchee, Florida, with an estimated age in her late 70s. She takes allergy medicine, iron supplements and omega 3 multivitamins, and has been trained to accept a nebulizer treatment for coughing.
Emerson, a Galapagos tortoise at the Toledo Zoo in Ohio, whose age is estimated at about 100.
Andrew Welsh-Huggins can be reached on Twitter at https://twitter.com/awhcolumbus. His work can be found at http://bigstory.ap.org/content/andrew-welsh-huggins
This story has been corrected to show that Tiki the giraffe is in Oakland, California, not San Francisco.
Office of the Vice President for Research
School of Medicine researchers publish findings that marijuana THC can delay transplant rejection
Three researchers with the USC School of Medicine’s prestigious Complementary Alternative Medicine Center have published a new scholarly article in the September 2015 issue of the Journal of Leukocyte Biology. Drs. Jessica Sido, Prakash Nagarkatti and Mitzi Nagarkatti’s article discusses their findings from a recent experiment which suggests that THC, the active ingredient in marijuana, may delay the rejection of incompatible organs.
Adding to this success, their research was also featured this week on the American Association for the Advancement of Science’s popular EurkeAlert website. Read the EurekAlert coverage here, and view the Journal of Leukocyte Biology article abstract here.