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Read our latest blog on interstate commerce from a compliance perspective

Interstate Commerce in the Hemp and THC Cannabis Industry

On this episode we are joined by Jini Glaros, Chief Scientific Officer at Modern Canna Labs

Ep 22, Part III: Decoding Cannabis Terminology with Jini Glaros

A retailer of hemp-derived cannabinoids, Sunmed | Your CBD Store (Los Angeles), an affiliate of Sunflora Inc., has 

regulations issued by Governor Gavin Newsom in California

. If the regulations are put into effect, the presence of any THC would be prohibited from hemp-derived products, and age restrictions would be placed on all hemp-derived products. According to Sunmed, the regulations effectively make 95% of the retailer’s inventory illegal, depriving consumers of wellness products they trust and rely on to support their health, as well as putting retailers at risk of closure, including Sunmed.

The justification for the regulations is to protect children, but Sunmed argues that current regulations already include safeguards for children, with the true problem being inadequate enforcement. The retailer says that it already uses child-proof packaging, 21+ age restrictions, warning labels, as well as batch specific third-party lab tests to ensure the safety of its products. By putting retailers at risk of closure, says Sunmed, the state is risking jobs and tax revenue. For example, Sunmed estimates that it has generated $11.5 million in sales since October 2021, contributing about $410,000 in state taxes, and creating hundreds of jobs.

"Every one of our California stores is expected to close if this overreaching regulation comes into effect. Meanwhile, illegal products sold at gas stations and headshops continue to get into the hands of children without enforced consequences," said Marcus Quinn, CEO of Sunmed | Your CBD Store, in a press release. The retailer is encouraging the hemp community to voice its concerns to Governor Newsom.

Articles

According to Sunmed, the regulations effectively make 95% of the retailer’s inventory illegal, depriving consumers of wellness products they trust and rely on to support their health, as well as putting retailers at risk of closure.

California Retailer, Sunmed, Issues Statement on Emergency Hemp Regulations

The Tennessee Growers Coalition (TGC) filed a lawsuit against the Tennessee Department of Agriculture (TDA) on Friday, September 6. The lawsuit challenges 

 issued by the agency on June 2024 that would establish a licensing program for retailers and suppliers of hemp-derived cannabinoid products. The licensing program was established on July 1, 2024, and TDA has issuing licenses and conducting outreach with plans to begin enforcement on October 1.

A law charging TDA with regulation of hemp-derived cannabinoids was passed in 

. TGC is challenging the law because TDA did not issue a Final Rule that took into consideration public comments. As TGC explains, after the law’s passage, a Final Rule was proposed by TDA in December of 2023, for which over 19,000 public comments were received, as well as hundreds of oral comments during a public hearing on February 6. However, instead of issued a Final Rule, the agency issued Emergency Rules, which TGC 

 violates the Tennessee Uniform Administrative Procedures Act. This act “forbids an agency from enacting emergency rules ‘based upon the agency’s failure to timely process and file rules through the normal rulemaking process,’” explains TGC.

TGC charges that TDA had three full months to prepare its proposed Final Rule for final release. “TGC Members’ businesses and livelihoods are at stake by being forced to adapt their business practices to regulations, change the type of products they sell, and how they manage compliance while paying a license fee under regulations that are void as a matter of law,” explains the group in a press release.

The lawsuit challenges Emergency Rules issued by the agency on June 2024 that would establish a licensing program for retailers and suppliers of hemp-derived cannabinoid products.

Tennessee Growers Coalition sues the Tennessee Department of Agriculture over Emergency Rules regulating hemp-derived cannabinoid products

On this three part episode of our Noid Knowledge podcast, host Evan Friedmann is joined by Jini Glaros, Chief Scientific Officer at Modern Canna Labs. They discuss  the importance of standardizing cannabis terminology to improve regulations, consumer education, and industry consistency; Jini's research comparing five moisture measurement techniques; the potential impact of Florida's cannabis legalization on the industry, and the complexities of cannabis contamination and microbial testing. 

Check out the video below for a quick Noid Factoid from Jini!

Catch up on all three parts of Episode 22:

Ep 22, Part I: Decoding Cannabis Terminology with Jini Glaros

Ep 22, Part II: Decoding Cannabis Terminology with Jini Glaros

Listen to a Noid Factoid from Jini Glaros, Chief Scientific Officer at Modern Canna Labs.

Noid Factoid from Episode 22

"My name is Jini Glaros, I am the CSO at Modern Canna Labs, and my Noid Factoid is that dried cannabis flower has a moisture content of five to 8% even though industry has typically and traditionally told us that that dried cannabis flower is 10 to 14% moisture."

 (1), Tilray Brands, a pharmaceutical and cannabis lifestyle company, announced the results of a case series examining the effect of cannabinoids in managing symptoms of fibromyalgia (FM). The 

 (2), titled, “Effectiveness of Cannabinoids Treatment in Pain Management and Other Fibromyalgia-Associated Symptoms: A Case Series,” was published in May 2024 in the 

Journal of Alternative Complementary & Integrative Medicine

, and was financially supported by Tilray Medical.

The study consisted of three patients with FM and analyzed the effect on their pain and other symptoms after being treated with Tilray Dried Flower THC18 (18% tetrahydrocannabinol) under medical direction. The medical cannabis was administered by vaporization for three months, and the patients were observed from July 2021 to September 2022.

According to the study, some of the noteworthy results include (2):

After one and three months of treatment, improvements were observed in Brief Pain Inventory, Visual Analogue Scale, Insomnia Severity Index, SF-36 Health Survey, and Fibromyalgia Impact Questionnaire, allowing pain relief, improved sleep quality, improved performance of daily life activities, and improved quality of life

Cannabinoids treatment allowed decreased co-medication in patients 1 and 2

Improvements of social interaction were  found in patients 1 and 3

Intercurrences and/or major adverse effects were not observed in any patient, but the tolerated doses varied greatly among these patients, indicating the need for a careful individual titration

"The findings of this study are encouraging and provide hope for fibromyalgia patients who are seeking effective treatments,” explained José Tempero, Tilray’s Medical Director, in the press release. “At Tilray, we are committed to conducting comprehensive scientific research that ensures our treatments are based on evidence and can improve patient care. We believe that these results represent a significant step forward in advancing the understanding of the therapeutic potential of cannabinoids and their role in managing chronic pain."

For limitations in the study, the researchers stated that cannabinoids administered by inhalation/vaporization are the only ones available in the country where the study took place, and this method of administration is associated with a greater occurrence of side effects.

The researchers also noted the strengths of the study including a treatment with a high concentration of THC, and the inclusion of patient-reported outcomes.

Tilray Brands, Tilray Medical Supports Scientific Study on Fibromyalgia With Positive Outcomes: Effectiveness of Cannabinoids Treatment in Pain Management and Other Fibromyalgia-Associated Symptoms, GlobeNewswire. 

https://www.globenewswire.com/en/news-release/2024/09/09/2942663/0/en/Tilray-Medical-Supports-Scientific-Study-on-Fibromyalgia-With-Positive-Outcomes-Effectiveness-of-Cannabinoids-Treatment-in-Pain-Management-and-Other-Fibromyalgia-Associated-Symptom.html

Tomás, SMS., Trincão, PRR. Effectiveness of Cannabinoids Treatment in Pain Management and Other Fibromyalgia-Associated Symptoms: A Case Series, 

https://www.heraldopenaccess.us/openaccess/effectiveness-of-cannabinoids-treatment-in-pain-management-and-other-fibromyalgia-associated-symptoms-a-case-series

A Tilray-funded case series found that cannabinoid treatment provided pain relief and improved other symptoms.

Cannabinoid Treatment for Fibromyalgia Symptom Management: Results from a Case Series

 examined how cannabinoids can be used as a therapeutic treatment for the chronic inflammatory disease, endometriosis (1). As explained in the study’s introduction, research suggests that the pathophysiology of the endocannabinoid system and endometriosis are connected. Researchers aimed to gauge how often cannabis was used to alleviate pain from endometriosis and if it helped reduce pain medication use.

Results from the cross-sectional survey, “Cannabis use in endometriosis: the patients have their say—an online survey for German-speaking countries,” were published in the 

The online survey was distributed via a direct link and also to endometriosis support groups through social media – the link was active from August to December 2022. Researchers analyzed responses from 912 of the participants, who were ages 18 and older and were living in Germany, Austria, and Switzerland. Cannabis use was illegal in the countries at the time the survey was conducted. As stated in the study, notable results included:

114 (17%) participants reported using cannabis for self-management of symptoms

Cannabis was rated as the most effective self-management strategy to reduce symptom intensity (self-rated efficacy 7.6 out of 10)

Additionally, about 90% of the participants were able to use cannabis to decrease their pain medication intake

The greatest improvement with cannabis use was observed in sleep (91%), menstrual pain (90%), and non-cyclical pelvic pain (80%)

Apart from increased fatigue (17%), side effects from using cannabis were infrequent (≤ 5%)

Researchers noted that previous data and studies on cannabis as a treatment for endometriosis is limited and does not support its use, yet surveys from various countries have revealed the self-managed use of cannabinoids for pain reduction. “Self-management strategies are commonly used in several parts of Europe, with cannabis being described as the most effective method for managing endometriosis-related symptoms,” the researchers explained. “The study indicates that there is a significant interest and demand for additional therapeutic options, and cannabis can potentially become an important part of a multimodal therapy approach for treating endometriosis.”

Most of the participants indicated that they would be interested in using a medical cannabis product (80% of respondents were interested in a CBD product and 66% for a THC product) to treat endometriosis symptoms, especially if prescribed by a physician, though prescribing cannabis has previously been proven to be a challenge in German-speaking countries.

Jasinski, V., Voltolini Velho, R., Sehouli, J. 

 Cannabis use in endometriosis: the patients have their say—an online survey for German-speaking countries. 

https://doi.org/10.1007/s00404-024-07652-6

Several participants reported symptom relief and reduced reliance on pain medication.

Cannabis and Managing Endometriosis Pain: Survey Highlights Patient Experiences

 (1), titled, “Delta-8 Tetrahydrocannabinol Exposures Reported to US Poison Centers: Variations Among US States and Regions and Associations with Public Policy,” is expressing the possibility that Delta-8 tetrahydrocannabinol (THC) products may be leading to a higher number of calls being made to poison control centers in states where cannabis is still considered illegal. Currently, the cannabis industry is unregulated with no uniform standards put in place. This can lead to significant variations in purity and potency in products (2). Researchers from Ohio State University’s College of Medicine (Columbus, Ohio) (2,3), reviewed data from the National Poison Data System (NPDS) during the time period of January 1, 2021, to December 31, 2022 where the primary substance was Delta-8 THC. The results showed that there were 4,925 exposures linked to Delta-8 THC. 69.8% of the exposures took place in the southern US (2).

The variables researchers investigated were, “Year, age group, sex, route of exposure (ingestion, inhalation, or other), reason for exposure, exposure type (single-substance or multiple-substance exposure), US region (Northeast, Midwest, South, and West), highest level of health care received, and medical outcome,” (3).

According to the study (2), “The rate of exposure per 100,000 US population increased by 79.2% from 0.53 in 2021 to 0.95 in 2022. In 2022, the mean rate of ∆8-THC exposures in states where cannabis use was illegal was 1.64 per 100,000 population (95% CI: 1.08-2.20) compared with 0.52 (95% CI: 0.29-0.76) in states where cannabis use was legal (P = 0.0010). In 2022, the mean rate of ∆8-THC exposures in states where ∆8-THC was unregulated was 1.36 per 100,000 population (95% CI: 0.95-1.77) compared with 0.17 (95% CI: 0.06-0.27) in states where ∆8-THC was banned (P < 0.0001).”

From the NPDS data, medical outcomes were analyzed via severity. For example, the study listed these outcomes by, “(1) no effect, (2) minor effect (minimal symptoms that generally resolve rapidly), (3) moderate effect (more pronounced, prolonged, or systemic symptoms than minor effect), (4) major effect (symptoms are life-threatening or result in significant disability or disfigurement), (5) death, (6) not followed (minimal clinical effects possible), (7) unrelated effect, or (8) unable to follow (judged as potentially toxic exposure). The category, ‘unable to follow (judged as potential toxic exposure),’ was considered unknown during analyses,” (3).

The research showed that a significant amount of Delta-8 THC exposures took place in the southern portion of the US (2). The states in this area, have for the most part, have not legalized cannabis and consider it illegal.

“The rate of ∆8-THC exposures reported to PCs [poison control centers] was significantly lower among states … where cannabis use was legal,” the study’s authors commented (2). “Consistent regulation of ∆8-THC across all states should be adopted.”

 reported that the 2018 Farm Bill entitled the US Food and Drug Administration (FDA) to regulate hemp-derived products (2). The organization has yet to utilize this ability. Regulators with the FDA claimed Congress is the establishment that needs to be creating a regulatory framework to watch over the “commercial production and marketing of hemp-derived cannabinoid products”, (2).

The conclusion researchers arrived at from the study was that Delta-8 THC exposures which were reported to US poison control centers rose 79% from 2021 to 2022 (1,3). Two-thirds of the cannabinoid exposures resulted in the southern portion of the US. States where cannabis was legalized showed a lower rate of Delta-8 THC exposures. The study’s final remarks were that, “Consistent regulation of ∆8-THC across all states should be adopted,” (1,3).

Smith, G. A.; Burgess, A.; Badeti, J.; Rine, N. I.; Gaw, C. E.; Middelberg, L. K.; Spiller, H. A.; Hays, H. L. Delta-8 tetrahydrocannabinol exposures reported to US Poison Centers: Variations among US states and regions and associations with public policy 

https://pubmed.ncbi.nlm.nih.gov/39168936/

Norml. More calls to poison control involving delta-8 products in states without legalization 

https://norml.org/news/2024/08/29/study-states-without-legal-access-to-cannabis-experience-elevated-rates-of-poison-control-incidents-involving-delta-8-thc-products/

Smith, G. A.; Burgess, A.; Badeti, J.; Rine, N. I.; Gaw, C. E.; Middelberg, L. K.; Spiller, H. A.; Hays, H. L. Delta-8 tetrahydrocannabinol exposures reported to US Poison Centers: Variations among US states and regions and associations with public policy - Journal of Medical Toxicology 

https://link.springer.com/article/10.1007/s13181-024-01030-z

Products containing Delta-8 THC may be leading to an increase in calls to poison control centers, according to a recent study.

States Without Legalized Cannabis Have Higher Rate of Poison Control Calls for Delta-8 THC Products, Says Recent Study

Photo © AdobeStock.com/ LIGHTFIELD STUDIOS

California Governor Gavin Newsom has issued 

 that would require food, beverages and dietary products that contain industrial hemp to have no detectable THC or other intoxicating cannabinoids per serving, limit the number of servings for hemp products to five, and create a minimum age of 21 to purchase hemp products. The rationale for the regulations, proposed by the California Department of Public Health (CDPH), is to protect youth from adverse effects related to products such as delta-8 THC.

“Intoxicating industrial hemp products can cause illness and injury to California consumers,” said Tomás Aragón, CDPH director and state public health officer, in a 

. “We are working to ensure products in the marketplace comply with state laws that protect consumers against these public health risks and have proposed emergency regulations that will improve protections for consumers.”

The regulations will take effect immediately upon approval from the Office of Administrative Law. Sellers will have to implement purchase restrictions and remove consumable hemp products with any detectable levels of THC from shelves. If the law is approved, regulators that include the Department of Public Health, the Department of Cannabis Control, the California Department of Alcoholic Beverage Control (ABC), the California Department of Tax and Fee Administration (CDTFA), and state and local law enforcement officials, will begin immediate enforcement action.

This action comes not long after the failure of 

 to pass the state’s senate. Industry has been highly critical of the bill, which would have place burdensome restrictions on hemp products, hurting manufacturers, retailers, and consumers.

"Today’s 'emergency' action by Governor Newsom is a betrayal of California hemp farmers, small businesses, and adult consumers. After having supported AB 45, which created a sound regulatory framework for the manufacture and sale of hemp products, Newsom’s Administration fell on the job and failed to take any steps to enforce it," said Jonathan Miller, general counsel for the U.S. Hemp Roundtable, in a statement. "Now, instead of addressing legitimate regulatory concerns shared by all good actors in the cannabis space – such as establishing reasonable policies to keep intoxicating products out of the hands of children – Governor Newsom instead has proposed a complete retail prohibition on 90-95% of popular hemp products for adults, including most non-intoxicating CBD products that he purports to support in his public communications. And in the middle of massive California budget deficits, he is unnecessarily throwing away nearly a quarter billion dollars in tax revenue from legitimate small businesses. We will be exploring all legal options in the coming days with California hemp farmers and businesses that comprise the multi-billion-dollar industry that this action would destroy."

The regulations would ban any hemp-derived food, beverage and dietary products from having any THC levels and impose an age restriction of 21 to purchase these products. 

Governor Newsom issues emergency regulations banning any level of THC from hemp-derived food and beverage products

Brian C. Smith, PhD, is Founder, CEO, and Chief Technical Officer of Big Sur Scientific. He is the inventor of the BSS series of patented mid-infrared based cannabis analyzers. Dr. Smith has done pioneering research and published numerous peer-reviewed papers on the application of mid-infrared spectroscopy to cannabis analysis, and sits on the editorial board of Cannabis Science and Technology. He has worked as a laboratory director for a cannabis extractor, as an analytical chemist for Waters Associates and PerkinElmer, and as an analytical instrument salesperson. He has more than 30 years of experience in chemical analysis and has written three books on the subject. Dr. Smith earned his PhD on physical chemistry from Dartmouth College. Direct correspondence to: 

In the first four installments of this calibration science series, we covered sources of error, signal-to-noise ratio (SNR), precision, accuracy, reducing noise, how to plot a calibration line, and how to measure calibration quality (1-4). In this, the fifth installment, we will continue the calibration quality control theme. Sometimes in a data set used to generate a calibration, one or more data points will stand out as being not like the others and these data points are called outliers. How to spot outliers and potential ways to correct them will be discussed here.

Back in the day on the American children’s show Sesame Street (5) they played the game “Which of These Things is Not Like the Others”. For example, they might show pictures of a duck, a hen, a pigeon, and a dog. In this case, the thing not like the others was the dog since it is a mammal and not a bird, making the dog an outlier. In calibration science spotting outliers is like this, spotting data points that are not like the others.

For our purposes we will limit ourselves to a discussion of outliers in the types of analyses performed in a cannabis analysis lab. Probably the most important thing measured in these labs is total tetrahydrocannabinol (THC) or potency. Two of the most common potency methods are high pressure liquid chromatography (HPLC) with ultraviolet-visible (UV-Vis) detection (6) and mid-infrared spectroscopy (7). In both these cases, spectral absorbance readings and concentration data are used to plot calibration lines. Thus, we will restrict our discussion to spotting concentration and spectral outliers.

A good way to spot concentration outliers is to first calculate a set of concentration residuals

 A concentration residual is the difference between the known and predicted concentration for a standard used in a calibration. This quantity is calculated using 

 is the concentration residual; C is the actual concentration; and C’ is the predicted concentration.

The concentration residual measures how well the concentration in a specific standard was predicted.

The next step in spotting concentration outliers is to plot the residuals versus sample number as seen in 

. The data in this case are for the isopropyl alcohol (IPA) calibration discussed in a previous column (4), thus the units of the residuals are volume percent IPA.

Under normal circumstances this plot should be a random scatter of points with no apparent structure and with the magnitude of all the residuals approximately the same. Note in the plot that for samples 1,3,4, and 5 the residuals are all right around 1% IPA, but that for sample 2 the residual is -15.9% IPA; this thing is certainly not like the others! This residual is 15 times bigger than the others.

Once we spot an outlier, the question we have to ask is whether to include that standard’s data in a calibration or not. Ideally, we need to find the assignable cause as to why something is an outlier. This term is statistics speak for the reason why something is an outlier. If we understand why something is an outlier, we can fix the problem or justify not using the data in a calibration.

In the case of sample 2 in Figure 1 the assignable cause was easy to find: I typed the wrong concentration value for sample 2 into the spreadsheet used to generate the calibration line. Correcting this typo gave the concentration residual plot seen in 

With the typo corrected the concentration residual for sample 2 was reduced from -15.9% IPA to 0.3% IPA, illustrating the power of concentration residual plots to improve calibrations.

There are a number of reasons why concentration outliers happen including:

1. Transcription Errors: In other words, typos. Often times the absorbance and concentration data for a calibration have to be typed into a spreadsheet or some other computer program. It is very easy to mess up the transcription of these numbers, i.e. to commit a typo. This is exactly what we saw with Figures 1 and 2 above.

2. Poorly made standards: In calibrations that use concentration data, the error in the known concentrations in the standards is often times the biggest source of error in the analysis, and lack of care and poor technique when making standards can condemn you to always having poor calibrations. Hence,anything you can do to improve the quality of known concentrations in your standards will pay dividends in calibration quality.

3. Sample Problems: If the concentration of the analyte in your standard changes between when you make the standard and when you measure its absorbance that is a problem. Things that can cause this to happen include reactions taking place within the sample, evaporation of the sample, or analyte precipitating out of the sample. A good way to check this problem is to monitor your standard samples over time. For instance, once you make a fresh standard measure its absorbance every few minutes, then hours, to see if it is stable or not.

Remember our calibration consists of concentration data and spectral absorbance data. Spotting concentration outliers involved calculating concentration residuals, similarly, spotting an outlier in the spectral absorbance data is done by calculating a spectral residual, the formula for which is seen in 

 is the spectral residual; A is the actual absorbance; and A’ is the predicted absorbance and where the actual and predicted absorbances may be peak heights or peak areas.

For the calculation of concentration residuals we had the predicted concentration, C’, already in our hands since we needed it to calculate calibration metrics. Where do we obtain the predicted absorbance? From the calibration line equation itself. The calibration line for our IPA method is seen in 

We discussed calibration lines in previous articles (1-4). Briefly, 0.165 is the slope of the calibration line, and -0.6834 is the 

-intercept. Since peak area (spectral absorbance) is on the 

-axis, if we know the concentration of any given IPA sample (X), we can calculate its corresponding peak area by plugging the concentration value into Equation 3 and then solving.

Now, to obtain the predicted peak area as needed for the spectral residual calculation we would use the predicted concentration as the X in Equation 3, and solving for Y would give us the predicted absorbance. The predicted absorbance represents the peak area the calibration says would correspond to a given predicted concentration.

For example, in Figure 2 the concentration residual for sample 1 is -1.4% IPA. The known concentration for sample 1 is 9% (4). If we rearrange Equation 1 we can solve for the predicted concentration as seen in 

In our example then C = 9%,
R = -1.4%, and the predicted concentration C’ is then 10.4%. To predict the peak area that corresponds to this concentration we set X = 10.4 in Equation 3 and to obtain 

to see that the predicted peak area that corresponds to a concentration of 10.4% IPA is 1.03. The right-hand column in 

 shows the measured peak areas for each IPA standard.

To calculate the spectral residual for the 5 standards used to determine the calibration line seen in Figure 3 one would repeat the exercise seen above for sample 1 for all 5 samples. This will yield a set of five spectral residuals. Like with concentration residuals, it is useful to plot spectral residuals versus sample number to look for outliers. Such a plot is seen in 

Note in Figure 4, that all the residuals are small, about the same magnitude, and do not have a discernible pattern. This is unlike Figure 1 where the sample with the concentration residual of -15.9% was clearly an outlier.

: Same as for concentration outliers, typos happen. This is the first thing to check when any outlier of any type is spotted.

: The peak height or area to be used in the calibration must be measured properly. More on that in a future column.

: Recall (1,2) that all measurements have noise/error, and this is true of spectra as well. Calibrations are always a garbage in/garbage out process, and noisy spectra will give inaccurate predicted concentrations. How to improve the SNR of spectra was discussed previously (1-4).

: Analytical instruments are finicky beasts and don’t always work properly leading to incorrectly measured data. Before using any analytical instrument for quantitative work make sure it has been calibrated, passed its quality control checks, and that you are following the method standard operating procedure (SOP) properly.

: If a molecule other than the analyte absorbs light at the same wavelength where we are measuring the peak height or area, this will interfere with the correct determination of the concentration of the analyte, hence the term interferents. Traditionally we dealt with interferents by making sure only the analyte contributed to the peak being used in the calibration. More recently, algorithmic methods known as chemometrics can get around the problem of interferents (8). However, this discussion is beyond the scope of this column series. Thus, for our purposes, it is important to choose a calibration peak that is known to be free of interferents.

: As always humans are fallible and make mistakes. Make sure the person using the instrument has been properly trained, the method has an SOP, and that it is followed properly.

What if There is No Assignable Cause for an Outlier?

This gets tricky. A data point may be an outlier because there is truly something wrong with the measurement, or it might contain information important for the calibration model that is not consistent with the other data points. Statisticians have spilled much ink as to what to do in this case, here is my rule of thumb based on my understanding of the literature. The first thing you should do is calculate the average of the residuals by using 

 is the average residual; i is the sample index; |R

| is the absolute value of an individual residual; and N is the number of residuals.

The purpose of using the absolute value is to keep positive and negative residual values from cancelling each other. For the five concentration residuals seen in Figure 2 their absolute values are 1.4, 0.3, 1.0, 0.2, and 0.9 % IPA, and their average is 0.76%.

In general, outliers whose residual is 10x that of the average can be discarded without an assignable cause, which would have been the case with the -15.6% concentration outlier, although we did find an assignable cause for it. Outliers of 3x or less should almost always be included in the calibration. The gray area is where the residual is >3x but <10x the residual average. In the absence of an assignable cause some judgement for these is needed. What I tend to do is remake the standard, measure its peak height or area, calculate its residual, and see if the residual value is reproducible. If so, I tend to keep this data point.

Outliers are data points in a calibration not like the others. They can be spotted by calculating residuals and plotting them versus sample number. Calculating the average residual and comparing it against individual residuals can be used to judge whether an outlier should be included or excluded from a calibration. Assignable causes of concentration and spectral outliers were discussed.

Smith, B., Calibration Science, Part I: Precision, Accuracy, and Random Error, 

Smith, B., Calibration Science, Part II: Systematic Error, Signal-to-Noise Ratios, and How to Reduce Random Error, 

Smith, B., Calibration Science, Part III: Calibration Lines and Correlation Coefficients, 

Smith, B., Calibration Science, Part IV: Calibration Metrics, 

https://en.wikipedia.org/wiki/Sesame_Street

Giese, M. E; Lewis, M. A.; Giese, L.; and Smith, K. M.; 

Smith, B., A Proposed Representative Sampling Plan for Hemp Grows, 

Quantitative Spectroscopy: Theory and Practice

Smith, B., Calibration Science, Part V: Spotting Outliers, 

, PhD, is Founder, CEO, and Chief Technical Officer of Big Sur Scientific. He is the inventor of the BSS series of patented mid-infrared based cannabis analyzers. Dr. Smith has done pioneering research and published numerous peer-reviewed papers on the application of mid-infrared spectroscopy to cannabis analysis, and sits on the editorial board of 

. He has worked as a laboratory director for a cannabis extractor, as an analytical chemist for Waters Associates and PerkinElmer, and as an analytical instrument salesperson. He has more than 30 years of experience in chemical analysis and has written three books on the subject. Dr. Smith earned his PhD on physical chemistry from Dartmouth College.
Direct correspondence to: 

Here, we discuss how to spot outliers and potential ways to correct them in data sets.

Calibration Science, Part V: Spotting Outliers

Recently, Custom Cones USA, a cannabis pre-roll packaging and manufacturing company, posted an analysis of their 

 on the current status of the pre roll market and its potential future direction, created in conjunction with cannabis industry data platform Headset. As noted by Custom Cones, infused pre rolls grew in popularity with consumers, becoming top sellers in 2023.

The white paper covers market trends, segment growth, production challenges, and more. For an understanding of recent activity in the pre roll market in the US, insights from Custom Cones’s retail data were combined with Headset’s point-of-sale data from 12 states (Arizona, California, Colorado, Illinois, Massachusetts, Maryland, Michigan, Missouri, Nevada, New York, Oregon, and Washington) from January 2023 to June 2024. Custom Cones’s data covered more than 300 businesses, from recreational cannabis producers to hemp producers, vertically integrated bands to multi-state operators, and more.

According to summaries of significant results compiled in a September 3, 2024 

Pre rolls amassed more than $4.1 billion in sales revenue and sold over 394 million units from January 2023 to June 2024.

The growth of the $4 billion pre-roll industry has propelled infused pre-rolls as a leading category, becoming the 3rd biggest cannabis category in the country, behind only flower and vape pens.

While premium pre-roll sales soar, pre-roll prices have actually dropped.

Pre-roll businesses ranked price, potency, and strain as the top three factors that weighed into consumers’ buying decisions around pre-rolls.

Custom Cones has previously published two white papers on the pre-roll market. “Every year we like to hunker down and look at the story the data is telling,” said Harrison Bard, Co-Founder and CEO of Custom Cones USA and DaySavers, in the press release. “Thanks to the help of our partners at Headset, we can now see even more clearly that pre-rolls are continuing to dominate the market on an upward trajectory that confirms our belief that pre-rolls remain a potent and profitable symbol of the cannabis industry as a whole. We hope this data can be used by producers, processors, and consumers alike to help make informed business and purchasing decisions.

Custom Cones USA, The State of the Pre Roll Market 2024, 

https://customconesusa.com/pre-roll-expert-knowledge-center/cannabis-preroll-industry-insights/#mainlink1

Custom Cones USA, Custom Cones USA White Paper Reveals Pre-Roll Industry Generated Over $4 Billion In Sales Revenue In Past Year and a Half. 

https://www.globenewswire.com/news-release/2024/09/03/2939761/0/en/Custom-Cones-USA-White-Paper-Reveals-Pre-Roll-Industry-Generated-Over-4-Billion-In-Sales-Revenue-In-Past-Year-and-a-Half.html

A recently published white paper delves into data on market and consumer trends for pre rolls.

Custom Cones USA Examines Data on the Current Pre Roll Market Industry

In indoor cannabis cultivation, increasing lighting penetration is crucial to maximize yield and ensure quality and consistent phytochemical content. Many factors influence how light penetrates the canopy, impacting photosynthesis and overall plant growth. We discuss methods to increase plant canopy penetration for indoor cannabis cultivation, increasing crop size while enhancing cannabinoid, terpene, and flavonoid production.

Shortcomings of Lighting in Indoor Horticulture

In the realm of cannabis cultivation, sunlight remains unmatched in its ability to penetrate plant canopies effectively. Despite advancements in indoor lighting technologies, these systems fail to achieve the same depth and uniformity of light penetration that sunlight provides. The inadequacies of lighting penetration in indoor horticulture can be attributed to deficiencies in lighting intensity, spectrum, and distribution, as well as thermal management of the grow environment. Moreover, certain plant functions, such as tropisms, photoreceptor and pigment protein saturation and activation, adversely influence light penetration, affecting plant health in indoor cannabis operations. For the purposes of this discussion, this paper addresses the use of full-spectrum light emitting diodes (LEDs) lighting in indoor grow operations. Although the term “full-spectrum” is used, LED lighting systems fall short of delivering the true full spectrum of light delivered by the sun.

Lighting intensity is a critical factor that directly influences photosynthesis, impacting yield and phytochemical composition in cannabis cultivation. Cannabis plants require a specific light intensity range for optimal growth. Insufficient lighting can stunt growth, reduce biomass, and accelerate leaf shedding by impairing photosynthesis and hormone signaling. Excessive light intensity can cause photoinhibition, which damages the photosynthetic apparatus and induces a stress response. Interestingly, these stress responses are not always detrimental; in some cases, they can lead to the enhanced production of secondary metabolites. Since these responses occur at the subcellular level, they present significant challenges for study and analysis (1).

Lighting intensity, quantified in micromoles per square meter per second (µmol/m²/s), is a fundamental metric in cannabis cultivation. During the vegetative growth phase, cannabis plants typically require light intensities ranging from 400-600 µmol/m²/s. This requirement increases to approximately 600-900 µmol/m²/s during the flowering stage to support flower development and resin production.For reference, sunlight within the Photosynthetically Active Radiation (PAR) spectrum of 400-700 nanometers (nm), strikes the Earth at an intensity of around 2000 µmol/m

In contrast, LED lighting seldom achieves intensities exceeding 1000 µmol/m

/s at the plant canopy, and when it does, the lighting footprint provided is very limited. Several factors influence LED lighting performance, including the efficacy of the LEDs, typically measured in lumens per Watt (lm/W), and the ability to control lighting output to achieve uniform coverage with minimal waste. Although the efficacy of LEDs is improving, the theoretical maximum for full-spectrum LEDs stands at 300-400 lumens per Watt (2).

Incorrect lighting placement is a common issue in cultivation. LED lighting has an output that is either too wide causing “spill” or wasted light that doesn’t strike the plant canopy, or too narrow, providing adequate lighting to only a limited portion of the plant canopy. The height at which lights are mounted is a critical factor as well, especially with horticultural fixtures that were designed to be mounted very close to the plant canopy. For instance, one manufacturer recommends a mounting height of 8 in above the plant tops. If this distance is doubled, the light intensity, and therefore photon delivery, decreases by 75% (refer to the Inverse Square Law for Lighting). This demonstrates how small variations of just a few inches can significantly change lighting delivery.

“Lighting spectrum” refers to the wavelengths emitted by a light source, encompassing the visible light spectrum and extending into the ultra-violet (UV) and infrared (IR) regions. Blue light (400-500 nm) is essential for vegetative growth, regulating stomatal opening and chlorophyll synthesis. Red light (600-700nm) is pivotal in driving photosynthesis and influencing flowering and photomorphology. Far Red light (700-800nm) increases growth and helps to regulate photoperiod. Amber light peaks at 620 nm and provides protective properties, which we identify later.

Despite the high configurability of LED spectrum delivery by manufacturers, their ability to compete with natural sunlight in terms of intensity and spectrum remains constrained by high costs and current technological limitations. Nevertheless, LED technology has significantly advanced, offering superior capabilities that far outweigh those of more traditional horticultural lighting solutions, such as High Pressure Sodium (HPS), Metal Halide (MH) including Ceramic Metal Halide (CMH), and fluorescent technologies. It is now common knowledge that LED lighting produces higher quality cannabis in greater yields than the industry’s previously adopted lighting solutions.

The advantages of LED lighting stem from its ability to tailor the light spectrum to the specific needs of cannabis plants at different growth stages. This generally requires a combination of broad-spectrum and discrete frequencies to create an optimal light recipe for cannabis growth. This means some frequencies are underserved while some frequencies may provide too much light. The underserved frequencies lack the power to penetrate deep into the canopy and maximize yields. On the other hand, the overabundant frequencies can lead to photoreceptor and pigment saturation, causing plants to activate protective mechanisms or suffer from growth and quality issues.

An overabundance of light can lead to the saturation of photoreactive plant elements, which play vital roles in growth, development and stress responses of plants. These elements include pigments such as chlorophyll, carotenoids, anthocyanins and flavonoids, as well as photoreceptors like phytochromes, cryptochromes, phytotropins and UVR8.

Chlorophyll, the most crucial pigment in plants, is essential for photosynthesis, where it converts light energy into chemical energy, transforming water (H2O) and carbon dioxide (CO

). Excessive light can saturate chlorophyll, causing growth to plateau and potentially damage leaves. Photoinhibition results when the plant's photosynthetic machinery is overwhelmed, decreasing photosynthesis efficiency and energy production. Photoinhibition can also generate reactive oxygen species (ROS), including free radicals and peroxides, which may oxidize vital cellular components like proteins, lipids, and nucleic acids, leading to significant cellular damage or death (4).

Carotenoids are critical for protecting chlorophyll from photooxidation and facilitating non-photochemical quenching—a process that turns excess light energy into heat. If this pigment experiences light saturation, carotenoids can undergo photobleaching. This degradation results in the loss of their color, light absorption capabilities, and antioxidant functions (5).

Anthocyanins absorb blue-green and ultraviolet light, functioning as photoreceptive agents to mitigate cellular damage. Additionally, they also produce red and blue hues in plants. However, when these pigments become saturated, their protective properties diminish, potentially leading to altered or faded coloration within the plant tissues (6).

Flavonoids, a diverse group of phytonutrients, encompass various pigments including anthocyanins, and are renowned for their antioxidant properties. They play a vital role in neutralizing ROS and protecting plant cells from oxidative stress. Prolonged exposure to excessive light can cause flavonoids to become saturated and could damage enzymatic pathways. This may also disrupt their structural integrity and functionality thus affecting the overall plant health and resilience.

Phytochromes are photoreceptors that are sensitive to red and far-red receptors. Phytochromes help regulate processes such as seed germination, stem elongation, leaf expansion, and the timing of flowering in response to changes in light conditions. During seed germination, where they detect light quality and quantity, which is crucial for breaking seed dormancy and initiating growth. They are also able to detect the light environment, distinguishing between shaded and full light conditions. Furthermore, phytochromes are integral in photoperiodism, influencing the timing of flowering based on day length.

Cryptochromes are photoreceptors that are sensitive to blue-light and to ultraviolet-A (UV-A) radiation.They control several functions, including seedling development, flowering time, and circadian rhythms. They play a crucial role in enabling plants to gauge the overall quality of light, important for growth and development.

Phototropins, another group of blue-light responsive photoreceptors are primarily involved in mediating phototropism—the growth of plant organs towards or away from light. They influence chloroplast movement, stomatal opening, and possibly light-induced water uptake mechanisms.

The saturation of these photoreceptors can lead to a range of issues, from altered growth patterns and developmental timing to reduced photosynthetic efficiency and stress responses.

The following discusses the importance of maintaining high photosynthetic photon flux density (PPFD) levels for optimal plant growth and details strategies to maximize light penetration within a plant canopy effectively. It highlights various methods to ensure plants receive sufficient light without risking light saturation or damage, essential for achieving high yields and superior phytochemical content in cannabis.

High PPFD levels ensure that plants receive adequate light for maximum photosynthetic activity, leading to higher yields, and higher quality phytochemical content. However, maintaining an optimal PPFD without causing light saturation or damage is crucial to plant function.

Here are the primary methods for maximizing canopy penetration without harming plants:

Use LED Luminaires: LEDs can increase penetration due to their lower waste heat output, allowing them to be placed closer to the plant canopy without causing heat stress. If purchasing new lighting, make sure you have enough lights to cover your crop correctly. Adjust the power settings to meet the PAR requirements for all stages of growth. Purchasing LED fixtures that utilize Total Internal Reflective lensing will further increase PPFD and penetration with minimal wasted light.

Optimize Light Placement and Mounting Height: Arrange your lights to maximize coverage over your canopy with minimal spill and wasted light. Use enough light fixtures to cover your crop, then increase your luminaire density until PAR values required by your plants for their specific stage of growth are met. Use an LED-specific extended PAR lighting meter (400-750 nm) to verify accuracy of your setup.

Use Under Lighting: Not a common practice but worth mentioning is the use of under-lighting specifically designed to illuminate plants from below is worth considering. Though a costly endeavor, it may prove advantageous for high-end boutique cultivation operations. Great care must be taken to ensure these lighting fixtures are built for the task: they should be water and dust proof, possess excellent thermal management to prevent LEDs from overheating, and include robust electrical protection.

Adjust Lighting Intensity as Plants Grow: Increasing light intensity gradually as plants mature can maintain highest penetration possible while minimizing light stress. There are several methods to accomplish this:

1. Some LED fixtures have dimming capabilities, either manually adjusted or automatically tuned via various equipment and applications. 

2. Traditionally, non-LED lighting technologies have required manual adjustment of height for each light. This can become quite a chore if the operation uses many lights.

3. Automated light movers can be used for height adjustment, but their use is generally not recommended due to their high cost and potential maintenance challenges.

4. To accomplish this task with minimal capital and operational (labor) costs, it is highly recommended to place lights at a height far enough above the plants to cause them to “stretch” into the lighting. As plants stretch towards the light source, PAR values will increase. Once plants reach their maturity height, the lights may be raised or lowered to tune the PAR values. After the first few crops run in your facility, with known genetics and specific light fixtures, growers can usually place lights and never have to touch them again during the flowering stages.

Use Reflective Materials: Use reflective surfaces to bounce light under and around plant canopies. Flat white paint covering walls and flooring is inexpensive and helps spread light evenly. For those using grow trays, some manufacturers build them in flat white for this purpose.

Control Plant Density and Canopy Management: Regularly tend plants to manage canopy density and branch positioning. Techniques like topping, low-stress training (LST), and defoliation can help create a more open canopy, allowing light to penetrate deeper. This not only improves light penetration but also air circulation.

Monitor and Adjust Environment: Ensure temperature, humidity, and CO

 levels are optimized. Waste heat (energy converted to heat instead of light) can increase leaf temperature, so adequate ventilation and air conditioning may be necessary to keep temperatures within an ideal range (typically 70-85° F during the light period). Monitor this by ensuring proper Vapor Pressure Deficit (VPD) is maintained (7).

A look at how some cultivation methods are used to increase plant canopy penetrationfor indoor cannabis cultivation, increasing crop size while enhancing cannabinoid, terpene, and flavonoid production.


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